<?xml version="1.0" encoding="ISO-8859-1"?><article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance">
<front>
<journal-meta>
<journal-id>0304-3584</journal-id>
<journal-title><![CDATA[Actualidades Biológicas]]></journal-title>
<abbrev-journal-title><![CDATA[Actu Biol]]></abbrev-journal-title>
<issn>0304-3584</issn>
<publisher>
<publisher-name><![CDATA[Instituto de Biología, Universidad de Antioquia]]></publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id>S0304-35842021000100001</article-id>
<article-id pub-id-type="doi">10.17533/udea.acbi.v43n114a01</article-id>
<title-group>
<article-title xml:lang="en"><![CDATA[Bone morphogenetic protein 2: heterologous expression and potential in bone regeneration]]></article-title>
<article-title xml:lang="es"><![CDATA[Proteína morfogenética de hueso 2: expresión heteróloga y potencial en la regeneración ósea]]></article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Mesa-Restrepo]]></surname>
<given-names><![CDATA[Andrea]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Fernando-Alzate]]></surname>
<given-names><![CDATA[Juan]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Patiño-Gonzalez]]></surname>
<given-names><![CDATA[Edwin Bairon]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
</contrib-group>
<aff id="Af1">
<institution><![CDATA[,Universidad de Antioquia  ]]></institution>
<addr-line><![CDATA[Medellín ]]></addr-line>
<country>Colombia</country>
</aff>
<aff id="Af2">
<institution><![CDATA[,Universidad de Antioquia Centro Nacional de Secuenciación Genómica ]]></institution>
<addr-line><![CDATA[Medellín ]]></addr-line>
<country>Colombia</country>
</aff>
<aff id="Af3">
<institution><![CDATA[,Universidad de Antioquia  ]]></institution>
<addr-line><![CDATA[Medellín ]]></addr-line>
<country>Colombia</country>
</aff>
<pub-date pub-type="pub">
<day>00</day>
<month>06</month>
<year>2021</year>
</pub-date>
<pub-date pub-type="epub">
<day>00</day>
<month>06</month>
<year>2021</year>
</pub-date>
<volume>43</volume>
<numero>114</numero>
<copyright-statement/>
<copyright-year/>
<self-uri xlink:href="http://www.scielo.org.co/scielo.php?script=sci_arttext&amp;pid=S0304-35842021000100001&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://www.scielo.org.co/scielo.php?script=sci_abstract&amp;pid=S0304-35842021000100001&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://www.scielo.org.co/scielo.php?script=sci_pdf&amp;pid=S0304-35842021000100001&amp;lng=en&amp;nrm=iso"></self-uri><abstract abstract-type="short" xml:lang="en"><p><![CDATA[Abstract Currently, bone morphogenetic protein 2 (BMP-2) is one of the two osteoinductive growth factors used in medical devices to promote bone formation. Typically, this protein is bought from commercial houses at high rates and in small quantities that are not enough to cover clinical needs. Because of this, it has been proposed that research centers use their own heterologous expression systems to have a constant supply of BMP-2. The aim of this study was to standardize the heterologous expression of BMP-2 and evaluate its osteoinductive activity in vitro. Our procedure for expression and purification was based on recombinant DNA technology using the plasmid pET-28 and IPTG as inductor. After extracting the protein from inclusion bodies, folding it and modifying it via a redox system, we observed via electrophoresis a 26 kDa dimer. We evaluated its osteoinductive activity in myoblastic *C2C12 by quantifying enzymatically the activity of alkaline phosphate (ALP) and staining mineralization nodules. ALP activity is proportional to BMP-2 concentration, increasing 90% at 3 µg/mL. These cells form calcium nodules, mineralizing 50% of the area.]]></p></abstract>
<abstract abstract-type="short" xml:lang="es"><p><![CDATA[Resumen Actualmente la proteína morfogénica ósea 2 (BMP-2) es uno de los dos factores de crecimiento más osteoinductivos usado clínicamente en dispositivos médicos que promueve la formación de hueso. Normalmente esta proteína es comprada a altos precios y en cantidades pequeñas que no alcanzan a cubrir las necesidades clínicas. Debido a esto, se ha propuesto que centros de investigación utilicen sus propios sistemas heterólogos para obtener un suministro constante. El objetivo de este trabajo es estandarizar la expresión heteróloga de la BMP-2 y evaluar su actividad osteoinductiva in vitro. Nuestro procedimiento para la expresión y purificación se basó en la tecnología de DNA recombinante usando el plásmido pET-28 e IPTG como inductor. Después de extraer la proteína de los cuerpos de inclusión, renaturalizarla y modificarla usando un sistema redox, se observó mediante electroforesis un dímero de 26 kDa. Se evaluó su actividad osteoinductiva en células mioblásticas C2C12 cuantificando enzimáticamente la actividad de la fosfatasa alcalina (ALP) y realizando una tinción de los nódulos de mineralización. La actividad de la fosfatasa alcalina fue proporcional a la concentración de BMP-2, obteniendo un aumento del 90% a concentraciones de 3 µg/mL. Estas células formaron nódulos de calcio, mineralizando un 50% la superficie.]]></p></abstract>
<kwd-group>
<kwd lng="en"><![CDATA[Alkaline phosphatase]]></kwd>
<kwd lng="en"><![CDATA[Cells C2C12]]></kwd>
<kwd lng="en"><![CDATA[Refolding protein]]></kwd>
<kwd lng="en"><![CDATA[rhBMP-2]]></kwd>
<kwd lng="es"><![CDATA[Células C2C12]]></kwd>
<kwd lng="es"><![CDATA[Fosfatasa alcalina]]></kwd>
<kwd lng="es"><![CDATA[Renaturalización]]></kwd>
<kwd lng="es"><![CDATA[rhBMP-2]]></kwd>
</kwd-group>
</article-meta>
</front><back>
<ref-list>
<ref id="B1">
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Allendorph]]></surname>
<given-names><![CDATA[G.P.]]></given-names>
</name>
<name>
<surname><![CDATA[Vale]]></surname>
<given-names><![CDATA[W.W.]]></given-names>
</name>
<name>
<surname><![CDATA[Choe]]></surname>
<given-names><![CDATA[S.]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Structure of the ternary signaling complex of a TGF-&#946; superfamily member]]></article-title>
<source><![CDATA[Proceedings of the National Academy of Sciences of the United States of America]]></source>
<year>2006</year>
<volume>103</volume>
<numero>20</numero>
<issue>20</issue>
<page-range>7643-8</page-range></nlm-citation>
</ref>
<ref id="B2">
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Bahney]]></surname>
<given-names><![CDATA[C.S.]]></given-names>
</name>
<name>
<surname><![CDATA[Zondervan]]></surname>
<given-names><![CDATA[R.L.]]></given-names>
</name>
<name>
<surname><![CDATA[Allison]]></surname>
<given-names><![CDATA[P.]]></given-names>
</name>
<name>
<surname><![CDATA[Theologis]]></surname>
<given-names><![CDATA[A.]]></given-names>
</name>
<name>
<surname><![CDATA[Ashley]]></surname>
<given-names><![CDATA[J.W.]]></given-names>
</name>
<name>
<surname><![CDATA[Ahn]]></surname>
<given-names><![CDATA[J.]]></given-names>
</name>
<name>
<surname><![CDATA[Miclau]]></surname>
<given-names><![CDATA[T.]]></given-names>
</name>
<name>
<surname><![CDATA[Marcucio]]></surname>
<given-names><![CDATA[R.S.]]></given-names>
</name>
<name>
<surname><![CDATA[Hankenson]]></surname>
<given-names><![CDATA[K.D.]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Cellular biology of fracture healing]]></article-title>
<source><![CDATA[Journal of Orthopaedic Research]]></source>
<year>2019</year>
<volume>37</volume>
<numero>1</numero>
<issue>1</issue>
<page-range>35-50</page-range></nlm-citation>
</ref>
<ref id="B3">
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Basak]]></surname>
<given-names><![CDATA[S.]]></given-names>
</name>
<name>
<surname><![CDATA[Paul Nobrega]]></surname>
<given-names><![CDATA[R.]]></given-names>
</name>
<name>
<surname><![CDATA[Tavella]]></surname>
<given-names><![CDATA[D.]]></given-names>
</name>
<name>
<surname><![CDATA[Deveau]]></surname>
<given-names><![CDATA[L. M.]]></given-names>
</name>
<name>
<surname><![CDATA[Koga]]></surname>
<given-names><![CDATA[N.]]></given-names>
</name>
<name>
<surname><![CDATA[Tatsumi-Koga]]></surname>
<given-names><![CDATA[R.]]></given-names>
</name>
<name>
<surname><![CDATA[Baker]]></surname>
<given-names><![CDATA[D.]]></given-names>
</name>
<name>
<surname><![CDATA[Massi]]></surname>
<given-names><![CDATA[F.]]></given-names>
</name>
<name>
<surname><![CDATA[Robert Matthews]]></surname>
<given-names><![CDATA[C.]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Networks of electrostatic and hydrophobic interactions modulate the complex folding free energy surface of a designed &#946;&#945; protein]]></article-title>
<source><![CDATA[Proceedings of the National Academy of Sciences of the United States of America]]></source>
<year>2019</year>
<volume>116</volume>
<numero>14</numero>
<issue>14</issue>
<page-range>6806-11</page-range></nlm-citation>
</ref>
<ref id="B4">
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[DeLano]]></surname>
<given-names><![CDATA[W.L.]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[PyMOL: An open-source molecular graphics tool]]></article-title>
<source><![CDATA[CCP4 Newsletter On Protein Crystallography]]></source>
<year>2002</year>
<volume>40</volume>
<page-range>82-92</page-range></nlm-citation>
</ref>
<ref id="B5">
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Durham]]></surname>
<given-names><![CDATA[E.L.]]></given-names>
</name>
<name>
<surname><![CDATA[Howie]]></surname>
<given-names><![CDATA[R.N.]]></given-names>
</name>
<name>
<surname><![CDATA[Hall]]></surname>
<given-names><![CDATA[S.]]></given-names>
</name>
<name>
<surname><![CDATA[Larson]]></surname>
<given-names><![CDATA[N.]]></given-names>
</name>
<name>
<surname><![CDATA[Oakes]]></surname>
<given-names><![CDATA[B.]]></given-names>
</name>
<name>
<surname><![CDATA[Houck]]></surname>
<given-names><![CDATA[R.]]></given-names>
</name>
<name>
<surname><![CDATA[Grey]]></surname>
<given-names><![CDATA[Z.]]></given-names>
</name>
<name>
<surname><![CDATA[Steed]]></surname>
<given-names><![CDATA[M.]]></given-names>
</name>
<name>
<surname><![CDATA[Larue]]></surname>
<given-names><![CDATA[A.C.]]></given-names>
</name>
<name>
<surname><![CDATA[Muise-Helmericks]]></surname>
<given-names><![CDATA[R.]]></given-names>
</name>
<name>
<surname><![CDATA[Cray]]></surname>
<given-names><![CDATA[J.]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Optimizing bone wound healing using BMP2 with absorbable collagen sponge and Talymed nanofiber scaffold 11 Medical and Health Sciences 1103 Clinical Sciences 09 Engineering 0903 Biomedical Engineering]]></article-title>
<source><![CDATA[Journal of Translational Medicine]]></source>
<year>2018</year>
<volume>16</volume>
<numero>1</numero>
<issue>1</issue>
<page-range>1-8</page-range></nlm-citation>
</ref>
<ref id="B6">
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Englander]]></surname>
<given-names><![CDATA[S.W.]]></given-names>
</name>
<name>
<surname><![CDATA[Mayne]]></surname>
<given-names><![CDATA[L.]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[The nature of protein folding pathways]]></article-title>
<source><![CDATA[Proceedings of the National Academy of Sciences of the United States of America]]></source>
<year>2014</year>
<volume>111</volume>
<numero>45</numero>
<issue>45</issue>
<page-range>15873-80</page-range></nlm-citation>
</ref>
<ref id="B7">
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Fung]]></surname>
<given-names><![CDATA[S.L.]]></given-names>
</name>
<name>
<surname><![CDATA[Wu]]></surname>
<given-names><![CDATA[X.]]></given-names>
</name>
<name>
<surname><![CDATA[Maceren]]></surname>
<given-names><![CDATA[J.P.]]></given-names>
</name>
<name>
<surname><![CDATA[Mao]]></surname>
<given-names><![CDATA[Y.]]></given-names>
</name>
<name>
<surname><![CDATA[Kohn]]></surname>
<given-names><![CDATA[J.]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[In vitro evaluation of recombinant bone morphogenetic protein-2 bioactivity for regenerative medicine]]></article-title>
<source><![CDATA[Tissue Engineering - Part C: Methods]]></source>
<year>2019</year>
<volume>25</volume>
<numero>9</numero>
<issue>9</issue>
<page-range>553-9</page-range></nlm-citation>
</ref>
<ref id="B8">
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Hettiaratchi]]></surname>
<given-names><![CDATA[M.H.]]></given-names>
</name>
<name>
<surname><![CDATA[Krishnan]]></surname>
<given-names><![CDATA[L.]]></given-names>
</name>
<name>
<surname><![CDATA[Rouse]]></surname>
<given-names><![CDATA[T.]]></given-names>
</name>
<name>
<surname><![CDATA[Chou]]></surname>
<given-names><![CDATA[C.]]></given-names>
</name>
<name>
<surname><![CDATA[McDevitt]]></surname>
<given-names><![CDATA[T.C.]]></given-names>
</name>
<name>
<surname><![CDATA[Guldberg]]></surname>
<given-names><![CDATA[R.E.]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Heparin-mediated delivery of bone morphogenetic protein-2 improves spatial localization of bone regeneration]]></article-title>
<source><![CDATA[Science Advances]]></source>
<year>2020</year>
<volume>6</volume>
<numero>1</numero>
<issue>1</issue>
<page-range>1-12</page-range></nlm-citation>
</ref>
<ref id="B9">
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Ihm]]></surname>
<given-names><![CDATA[H.J.]]></given-names>
</name>
<name>
<surname><![CDATA[Yang]]></surname>
<given-names><![CDATA[S.-J.]]></given-names>
</name>
<name>
<surname><![CDATA[Huh]]></surname>
<given-names><![CDATA[J.-W.]]></given-names>
</name>
<name>
<surname><![CDATA[Choi]]></surname>
<given-names><![CDATA[S.Y.]]></given-names>
</name>
<name>
<surname><![CDATA[Cho]]></surname>
<given-names><![CDATA[S.-W.]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Soluble expression and purification of synthetic human bone morphogenetic protein-2 in Escherichia coli]]></article-title>
<source><![CDATA[BMB Reports]]></source>
<year>2008</year>
<volume>41</volume>
<numero>5</numero>
<issue>5</issue>
<page-range>404-7</page-range></nlm-citation>
</ref>
<ref id="B10">
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Kashiwagi]]></surname>
<given-names><![CDATA[K.]]></given-names>
</name>
<name>
<surname><![CDATA[Tsuji]]></surname>
<given-names><![CDATA[T.]]></given-names>
</name>
<name>
<surname><![CDATA[Shiba]]></surname>
<given-names><![CDATA[K.]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Directional BMP-2 for functionalization of titanium surfaces]]></article-title>
<source><![CDATA[Biomaterials]]></source>
<year>2009</year>
<volume>30</volume>
<numero>6</numero>
<issue>6</issue>
<page-range>1166-75</page-range></nlm-citation>
</ref>
<ref id="B11">
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Kim]]></surname>
<given-names><![CDATA[H.S.]]></given-names>
</name>
<name>
<surname><![CDATA[Neugebauer]]></surname>
<given-names><![CDATA[J.]]></given-names>
</name>
<name>
<surname><![CDATA[McKnite]]></surname>
<given-names><![CDATA[A.]]></given-names>
</name>
<name>
<surname><![CDATA[Tilak]]></surname>
<given-names><![CDATA[A.]]></given-names>
</name>
<name>
<surname><![CDATA[Christian]]></surname>
<given-names><![CDATA[J.L.]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[BMP7 functions predominantly as a heterodimer with BMP2 or BMP4 during mammalian embryogenesis]]></article-title>
<source><![CDATA[ELife]]></source>
<year>2019</year>
<volume>8</volume>
<page-range>1-22</page-range></nlm-citation>
</ref>
<ref id="B12">
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Krauss]]></surname>
<given-names><![CDATA[I.R.]]></given-names>
</name>
<name>
<surname><![CDATA[Merlino]]></surname>
<given-names><![CDATA[A.]]></given-names>
</name>
<name>
<surname><![CDATA[Vergara]]></surname>
<given-names><![CDATA[A.]]></given-names>
</name>
<name>
<surname><![CDATA[Sica]]></surname>
<given-names><![CDATA[F.]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[An overview of biological macromolecule crystallization]]></article-title>
<source><![CDATA[International Journal of Molecular Sciences]]></source>
<year>2013</year>
<volume>14</volume>
<numero>6</numero>
<issue>6</issue>
<page-range>11643-91</page-range></nlm-citation>
</ref>
<ref id="B13">
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Krishnakumar]]></surname>
<given-names><![CDATA[G.S.]]></given-names>
</name>
<name>
<surname><![CDATA[Roffi]]></surname>
<given-names><![CDATA[A.]]></given-names>
</name>
<name>
<surname><![CDATA[Reale]]></surname>
<given-names><![CDATA[D.]]></given-names>
</name>
<name>
<surname><![CDATA[Kon]]></surname>
<given-names><![CDATA[E.]]></given-names>
</name>
<name>
<surname><![CDATA[Filardo]]></surname>
<given-names><![CDATA[G.]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Clinical application of bone morphogenetic proteins for bone healing: a systematic review]]></article-title>
<source><![CDATA[International Orthopedics]]></source>
<year>2017</year>
<volume>41</volume>
<page-range>1073-83</page-range></nlm-citation>
</ref>
<ref id="B14">
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Long]]></surname>
<given-names><![CDATA[S.]]></given-names>
</name>
<name>
<surname><![CDATA[Truong]]></surname>
<given-names><![CDATA[L.]]></given-names>
</name>
<name>
<surname><![CDATA[Bennett]]></surname>
<given-names><![CDATA[K.]]></given-names>
</name>
<name>
<surname><![CDATA[Phillips]]></surname>
<given-names><![CDATA[A.]]></given-names>
</name>
<name>
<surname><![CDATA[Wong-Staal]]></surname>
<given-names><![CDATA[F.]]></given-names>
</name>
<name>
<surname><![CDATA[Ma]]></surname>
<given-names><![CDATA[H.]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Expression, purification, and renaturation of bone morphogenetic protein-2 from Escherichia coli]]></article-title>
<source><![CDATA[Protein Expression and Purification]]></source>
<year>2006</year>
<volume>46</volume>
<numero>2</numero>
<issue>2</issue>
<page-range>374-8</page-range></nlm-citation>
</ref>
<ref id="B15">
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Mevel]]></surname>
<given-names><![CDATA[R.]]></given-names>
</name>
<name>
<surname><![CDATA[Draper]]></surname>
<given-names><![CDATA[J.E.]]></given-names>
</name>
<name>
<surname><![CDATA[Lie-A-Ling]]></surname>
<given-names><![CDATA[M.]]></given-names>
</name>
<name>
<surname><![CDATA[Kouskoff]]></surname>
<given-names><![CDATA[V.]]></given-names>
</name>
<name>
<surname><![CDATA[Lacaud]]></surname>
<given-names><![CDATA[G.]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[RUNX transcription factors: Orchestrators of development]]></article-title>
<source><![CDATA[Development (Cambridge)]]></source>
<year>2019</year>
<volume>146</volume>
<page-range>1-19</page-range></nlm-citation>
</ref>
<ref id="B16">
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Miyazono]]></surname>
<given-names><![CDATA[K.]]></given-names>
</name>
<name>
<surname><![CDATA[Kamiya]]></surname>
<given-names><![CDATA[Y.]]></given-names>
</name>
<name>
<surname><![CDATA[Morikawa]]></surname>
<given-names><![CDATA[M.]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Bone morphogenetic protein receptors and signal transduction]]></article-title>
<source><![CDATA[Journal of Biochemistry]]></source>
<year>2010</year>
<volume>147</volume>
<numero>1</numero>
<issue>1</issue>
<page-range>35-51</page-range></nlm-citation>
</ref>
<ref id="B17">
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Mueller]]></surname>
<given-names><![CDATA[T.D.]]></given-names>
</name>
<name>
<surname><![CDATA[Nickel]]></surname>
<given-names><![CDATA[J.]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Promiscuity and specificity in BMP receptor activation]]></article-title>
<source><![CDATA[FEBS Letters]]></source>
<year>2012</year>
<volume>586</volume>
<numero>14</numero>
<issue>14</issue>
<page-range>1846-59</page-range></nlm-citation>
</ref>
<ref id="B18">
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Nickel]]></surname>
<given-names><![CDATA[J.]]></given-names>
</name>
<name>
<surname><![CDATA[Mueller]]></surname>
<given-names><![CDATA[T.D.]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Specification of BMP Signaling]]></article-title>
<source><![CDATA[Cells]]></source>
<year>2019</year>
<volume>8</volume>
<numero>12</numero>
<issue>12</issue>
<page-range>1579</page-range></nlm-citation>
</ref>
<ref id="B19">
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Park]]></surname>
<given-names><![CDATA[S.Y.]]></given-names>
</name>
<name>
<surname><![CDATA[Kim]]></surname>
<given-names><![CDATA[K.H.]]></given-names>
</name>
<name>
<surname><![CDATA[Kim]]></surname>
<given-names><![CDATA[S.]]></given-names>
</name>
<name>
<surname><![CDATA[Lee]]></surname>
<given-names><![CDATA[Y.M.]]></given-names>
</name>
<name>
<surname><![CDATA[Seol]]></surname>
<given-names><![CDATA[Y.J.]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[BMP-2 gene delivery-based bone regeneration in dentistry]]></article-title>
<source><![CDATA[Pharmaceutics]]></source>
<year>2019</year>
<volume>11</volume>
<numero>8</numero>
<issue>8</issue>
<page-range>1-23</page-range></nlm-citation>
</ref>
<ref id="B20">
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Rahman]]></surname>
<given-names><![CDATA[M.S.]]></given-names>
</name>
<name>
<surname><![CDATA[Akhtar]]></surname>
<given-names><![CDATA[N.]]></given-names>
</name>
<name>
<surname><![CDATA[Jamil]]></surname>
<given-names><![CDATA[H.M.]]></given-names>
</name>
<name>
<surname><![CDATA[Banik]]></surname>
<given-names><![CDATA[R.S.]]></given-names>
</name>
<name>
<surname><![CDATA[Asaduzzaman]]></surname>
<given-names><![CDATA[S.M.]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[TGF-&#946;/BMP signaling and other molecular events: Regulation of osteoblastogenesis and bone formation]]></article-title>
<source><![CDATA[Bone Research]]></source>
<year>2015</year>
<volume>3</volume>
</nlm-citation>
</ref>
<ref id="B21">
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Ruehle]]></surname>
<given-names><![CDATA[M.A.]]></given-names>
</name>
<name>
<surname><![CDATA[Krishnan]]></surname>
<given-names><![CDATA[L.]]></given-names>
</name>
<name>
<surname><![CDATA[Vantucci]]></surname>
<given-names><![CDATA[C.E.]]></given-names>
</name>
<name>
<surname><![CDATA[Wang]]></surname>
<given-names><![CDATA[Y.]]></given-names>
</name>
<name>
<surname><![CDATA[Stevens]]></surname>
<given-names><![CDATA[H.Y.]]></given-names>
</name>
<name>
<surname><![CDATA[Roy]]></surname>
<given-names><![CDATA[K.]]></given-names>
</name>
<name>
<surname><![CDATA[Guldberg]]></surname>
<given-names><![CDATA[R.E.]]></given-names>
</name>
<name>
<surname><![CDATA[Willett]]></surname>
<given-names><![CDATA[N.J.]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Effects of BMP-2 dose and delivery of microvascular fragments on healing of bone defects with concomitant volumetric muscle loss]]></article-title>
<source><![CDATA[Journal of Orthopaedic Research]]></source>
<year>2019</year>
<volume>37</volume>
<numero>3</numero>
<issue>3</issue>
<page-range>553-61</page-range></nlm-citation>
</ref>
<ref id="B22">
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Ruppert]]></surname>
<given-names><![CDATA[R.]]></given-names>
</name>
<name>
<surname><![CDATA[Hoffmann]]></surname>
<given-names><![CDATA[E.]]></given-names>
</name>
<name>
<surname><![CDATA[Sebald]]></surname>
<given-names><![CDATA[W.]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Human bone morphogenetic protein 2 contains a heparin-binding site which modifies its biological activity]]></article-title>
<source><![CDATA[European Journal of Biochemistry]]></source>
<year>1996</year>
<volume>237</volume>
<numero>1</numero>
<issue>1</issue>
<page-range>295-302</page-range></nlm-citation>
</ref>
<ref id="B23">
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Saraff]]></surname>
<given-names><![CDATA[V.]]></given-names>
</name>
<name>
<surname><![CDATA[Narayanan]]></surname>
<given-names><![CDATA[V.K.]]></given-names>
</name>
<name>
<surname><![CDATA[Lawson]]></surname>
<given-names><![CDATA[A.J.]]></given-names>
</name>
<name>
<surname><![CDATA[Shaw]]></surname>
<given-names><![CDATA[N.J.]]></given-names>
</name>
<name>
<surname><![CDATA[Preece]]></surname>
<given-names><![CDATA[M.A.]]></given-names>
</name>
<name>
<surname><![CDATA[Högler]]></surname>
<given-names><![CDATA[W.]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[A diagnostic algorithm for children with low alkaline phosphatase activities: Lessons learned from laboratory screening for hypophosphatasia]]></article-title>
<source><![CDATA[Journal of Pediatrics]]></source>
<year>2016</year>
<volume>172</volume>
<page-range>181-186e1</page-range></nlm-citation>
</ref>
<ref id="B24">
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Scheufler]]></surname>
<given-names><![CDATA[C.]]></given-names>
</name>
<name>
<surname><![CDATA[Sebald]]></surname>
<given-names><![CDATA[W.]]></given-names>
</name>
<name>
<surname><![CDATA[Hulsmeyer]]></surname>
<given-names><![CDATA[M.]]></given-names>
</name>
<name>
<surname><![CDATA[Hu]]></surname>
<given-names><![CDATA[M.]]></given-names>
</name>
<name>
<surname><![CDATA[Hülsmeyer]]></surname>
<given-names><![CDATA[M.]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Crystal Structure of Human Bone Morphogenetic Protein-2 at 2.7 A Resolution]]></article-title>
<source><![CDATA[Journal of Molecular Biology]]></source>
<year>1999</year>
<volume>287</volume>
<page-range>103-15</page-range></nlm-citation>
</ref>
<ref id="B25">
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Sharapova]]></surname>
<given-names><![CDATA[N.E.]]></given-names>
</name>
<name>
<surname><![CDATA[Kotnova]]></surname>
<given-names><![CDATA[A.P.]]></given-names>
</name>
<name>
<surname><![CDATA[Galushkina]]></surname>
<given-names><![CDATA[Z.M.]]></given-names>
</name>
<name>
<surname><![CDATA[Lavrova]]></surname>
<given-names><![CDATA[N.V.]]></given-names>
</name>
<name>
<surname><![CDATA[Poletaeva]]></surname>
<given-names><![CDATA[N.N.]]></given-names>
</name>
<name>
<surname><![CDATA[Tukhvatulin]]></surname>
<given-names><![CDATA[A.E.]]></given-names>
</name>
<name>
<surname><![CDATA[Semikhin]]></surname>
<given-names><![CDATA[A.S.]]></given-names>
</name>
<name>
<surname><![CDATA[Gromov]]></surname>
<given-names><![CDATA[A.V.]]></given-names>
</name>
<name>
<surname><![CDATA[Soboleva]]></surname>
<given-names><![CDATA[L.A.]]></given-names>
</name>
<name>
<surname><![CDATA[Ershova]]></surname>
<given-names><![CDATA[A.S.]]></given-names>
</name>
<name>
<surname><![CDATA[Zaitsev]]></surname>
<given-names><![CDATA[V.V.]]></given-names>
</name>
<name>
<surname><![CDATA[Sergienko]]></surname>
<given-names><![CDATA[O.V.]]></given-names>
</name>
<name>
<surname><![CDATA[Lunin]]></surname>
<given-names><![CDATA[V.G.]]></given-names>
</name>
<name>
<surname><![CDATA[Karyagina]]></surname>
<given-names><![CDATA[A.S.]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Production of the recombinant human bone morphogenetic protein-2 in Escherichia coli and testing of its biological activity in vitro and in vivo]]></article-title>
<source><![CDATA[Molecular Biology]]></source>
<year>2010</year>
<volume>44</volume>
<numero>6</numero>
<issue>6</issue>
<page-range>923-30</page-range></nlm-citation>
</ref>
<ref id="B26">
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Tabisz]]></surname>
<given-names><![CDATA[B.]]></given-names>
</name>
<name>
<surname><![CDATA[Schmitz]]></surname>
<given-names><![CDATA[W.]]></given-names>
</name>
<name>
<surname><![CDATA[Schmitz]]></surname>
<given-names><![CDATA[M.]]></given-names>
</name>
<name>
<surname><![CDATA[Luehmann]]></surname>
<given-names><![CDATA[T.]]></given-names>
</name>
<name>
<surname><![CDATA[Heusler]]></surname>
<given-names><![CDATA[E.]]></given-names>
</name>
<name>
<surname><![CDATA[Rybak]]></surname>
<given-names><![CDATA[J.]]></given-names>
</name>
<name>
<surname><![CDATA[Meinel]]></surname>
<given-names><![CDATA[L.]]></given-names>
</name>
<name>
<surname><![CDATA[Fiebig]]></surname>
<given-names><![CDATA[J.E.]]></given-names>
</name>
<name>
<surname><![CDATA[Mueller]]></surname>
<given-names><![CDATA[T.D.]]></given-names>
</name>
<name>
<surname><![CDATA[Nickel]]></surname>
<given-names><![CDATA[J.]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Site-Directed Immobilization of BMP-2: Two Approaches for the Production of Innovative Osteoinductive Sca ff olds]]></article-title>
<source><![CDATA[Biomacromolecules]]></source>
<year>2017</year>
<volume>18</volume>
<numero>3</numero>
<issue>3</issue>
<page-range>695-708</page-range></nlm-citation>
</ref>
<ref id="B27">
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Uday]]></surname>
<given-names><![CDATA[S.]]></given-names>
</name>
<name>
<surname><![CDATA[Matsumura]]></surname>
<given-names><![CDATA[T.]]></given-names>
</name>
<name>
<surname><![CDATA[Saraff]]></surname>
<given-names><![CDATA[V.]]></given-names>
</name>
<name>
<surname><![CDATA[Saito]]></surname>
<given-names><![CDATA[S.]]></given-names>
</name>
<name>
<surname><![CDATA[Orimo]]></surname>
<given-names><![CDATA[H.]]></given-names>
</name>
<name>
<surname><![CDATA[Högler]]></surname>
<given-names><![CDATA[W.]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Tissue non-specific alkaline phosphatase activity and mineralization capacity of bi-allelic mutations from severe perinatal and asymptomatic hypophosphatasia phenotypes: Results from an in vitro mutagenesis model]]></article-title>
<source><![CDATA[Bone]]></source>
<year>2019</year>
<volume>127</volume>
<numero>January</numero>
<issue>January</issue>
<page-range>9-16</page-range></nlm-citation>
</ref>
<ref id="B28">
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Vallejo]]></surname>
<given-names><![CDATA[L.F.]]></given-names>
</name>
<name>
<surname><![CDATA[Brokelmann]]></surname>
<given-names><![CDATA[M.]]></given-names>
</name>
<name>
<surname><![CDATA[Marten]]></surname>
<given-names><![CDATA[S.]]></given-names>
</name>
<name>
<surname><![CDATA[Trappe]]></surname>
<given-names><![CDATA[S.]]></given-names>
</name>
<name>
<surname><![CDATA[Cabrera-Crespo]]></surname>
<given-names><![CDATA[J.]]></given-names>
</name>
<name>
<surname><![CDATA[Andrea Hoffmann]]></surname>
<given-names><![CDATA[A.]]></given-names>
</name>
<name>
<surname><![CDATA[Gross]]></surname>
<given-names><![CDATA[G.]]></given-names>
</name>
<name>
<surname><![CDATA[Weich]]></surname>
<given-names><![CDATA[H.A.]]></given-names>
</name>
<name>
<surname><![CDATA[Rinas]]></surname>
<given-names><![CDATA[U.]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Renaturation and purification of bone morphogenetic protein-2 produced as inclusion bodies in high-cell-density cultures of recombinant Escherichia coli]]></article-title>
<source><![CDATA[Journal of Biotechnology]]></source>
<year>2002</year>
<volume>94</volume>
<numero>2</numero>
<issue>2</issue>
<page-range>185-94</page-range></nlm-citation>
</ref>
<ref id="B29">
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Von Einem]]></surname>
<given-names><![CDATA[S.]]></given-names>
</name>
<name>
<surname><![CDATA[Schwarz]]></surname>
<given-names><![CDATA[E.]]></given-names>
</name>
<name>
<surname><![CDATA[Rudolph]]></surname>
<given-names><![CDATA[R.]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[A novel TWO-STEP renaturation procedure for efficient production of recombinant BMP-2]]></article-title>
<source><![CDATA[Protein Expression and Purification]]></source>
<year>2010</year>
<volume>73</volume>
<numero>1</numero>
<issue>1</issue>
<page-range>65-9</page-range></nlm-citation>
</ref>
<ref id="B30">
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Xiong]]></surname>
<given-names><![CDATA[S.]]></given-names>
</name>
<name>
<surname><![CDATA[Zhang]]></surname>
<given-names><![CDATA[L.]]></given-names>
</name>
<name>
<surname><![CDATA[He]]></surname>
<given-names><![CDATA[Q.-Y.]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Fractionation of proteins by heparin chromatography]]></article-title>
<source><![CDATA[Methods in Molecular Biology (Clifton, N.J.)]]></source>
<year>2008</year>
<volume>424</volume>
<page-range>213-21</page-range></nlm-citation>
</ref>
<ref id="B31">
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Yilgor]]></surname>
<given-names><![CDATA[P.]]></given-names>
</name>
<name>
<surname><![CDATA[Tuzlakoglu]]></surname>
<given-names><![CDATA[K.]]></given-names>
</name>
<name>
<surname><![CDATA[Reis]]></surname>
<given-names><![CDATA[R. L.]]></given-names>
</name>
<name>
<surname><![CDATA[Hasirci]]></surname>
<given-names><![CDATA[N.]]></given-names>
</name>
<name>
<surname><![CDATA[Hasirci]]></surname>
<given-names><![CDATA[V.]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Incorporation of a sequential BMP-2/BMP-7 delivery system into chitosan-based scaffolds for bone tissue engineering]]></article-title>
<source><![CDATA[Biomaterials]]></source>
<year>2009</year>
<volume>30</volume>
<numero>21</numero>
<issue>21</issue>
<page-range>3551-9</page-range></nlm-citation>
</ref>
</ref-list>
</back>
</article>
