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Among several signaling pathways involved, mitogen\u2010activated protein kinases (MAPKs) have been reported to play a critical role. Magnesium (Mg)\u2010based alloys, including Mg\u2013Zn alloy, have been used clinically as implants in the musculoskeletal field and could promote BMSC osteogenic differentiation. However, the underlying mechanisms remain unclear. In this study, we produced Mg\u2013Zn alloy consists of Mg and low concentrations of Zn, calcium carbonate, and \u03b2\u2010tricalcium phosphate (\u03b2\u2010TCP; manifesting process not shown), prepared Mg, Zn, and Mg\u2013Zn extracts, and investigated the specific effects of these extracts on human BMSC (hBMSC) osteogenic differentiation and MAPK signaling. Mg extracts and Mg\u2013Zn extracts could significantly promote the osteogenic differentiation of hBMSCs as manifested as increased alkaline phosphatase levels, enhanced calcium nodules formation, and increased messenger RNA expression and protein levels of osteogenesis markers, including BMPs, Col\u2010I, Runx2, and Osx; in the meantime, Mg culture medium (CM) and Mg\u2013Zn CM both significantly enhanced the activation of MAPK signaling in hBMSCs. By adding ERK1\/2 signaling, p38 signaling, or JNK signaling inhibitor to Mg\u2013Zn CM, or conducting p38 MAPK silence in hBMSCs, we revealed that these extracts might promote hBMSC osteogenic differentiation via p38 MAPK signaling and MAPK\u2010regulated Runx2\/Osx. In conclusion, Mg<jats:sup>2+<\/jats:sup> in \u03b2\u2010TCP\/Mg\u2013Zn extract promotes the osteogenic differentiation of hBMSCs via MAPK\u2010regulated Runx2\/Osx interaction.<\/jats:p>","DOI":"10.1002\/jcp.29395","type":"journal-article","created":{"date-parts":[[2019,11,19]],"date-time":"2019-11-19T18:28:54Z","timestamp":1574188134000},"page":"5182-5191","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":61,"title":["Mg<sup>2+<\/sup> in \u03b2\u2010TCP\/Mg\u2013Zn composite enhances the differentiation of human bone marrow stromal cells into osteoblasts through MAPK\u2010regulated Runx2\/Osx"],"prefix":"10.1002","volume":"235","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3232-6473","authenticated-orcid":false,"given":"Zhenting","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Emergency Medicine The Second Xiangya Hospital, Central South University  Changsha Hunan China"},{"name":"Department of Urology Surgery Haikou People's Hospital\/Affiliated Haikou Hospital of Xiangya Medical College, Central South University  Haikou Hainan China"},{"name":"Department of Spine Surgery The Second Xiangya Hospital, Central South University  Changsha Hunan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Spine Surgery The Second Xiangya Hospital, Central South University  Changsha Hunan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Congcong","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Spine Surgery The Second Xiangya Hospital, Central South University  Changsha Hunan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Spine Surgery The Second Xiangya Hospital, Central South University  Changsha Hunan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingying","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine The Second Xiangya Hospital, Central South University  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohua","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine The Second Xiangya Hospital, Central South University  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianshi","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine The Second Xiangya Hospital, Central South University  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youwen","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine The Second Xiangya Hospital, Central South University  Changsha Hunan China"},{"name":"Department of Spine Surgery The Second Xiangya Hospital, Central South University  Changsha Hunan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,11,19]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M701116200"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.576793"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.4161\/21592527.2014.967616"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2007-0520"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/35065000"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2015.02.010"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joms.2014.09.007"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20100323"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00167-014-3325-6"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.040980"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.injury.2014.04.002"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2015.09.008"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2016.09.003"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.scs.0000170449.72040.ee"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.13.9645"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2014.05.074"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1205937"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M211386200"},{"issue":"5","key":"e_1_2_7_20_1","first-page":"476","article-title":"Tectorigenin promotes osteoblast differentiation and in vivo bone healing, but suppresses osteoclast differentiation and in vivo bone resorption","volume":"41","author":"Lee S. 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