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The appropriate physical activity and exercise could help attenuate bone loss, effectively stimulate bone formation, increase bone mineral density (BMD), prevent the progression of osteoporosis, and reduce the risk of bone fractures. Bone morphogenetic protein (BMP) is originally discovered as a protein with heterotopic bone-inducing activity in the bone matrix that exerts a critical role in multiple stages of bone metabolism. In the present study, the medium-intensity treadmill exercise enhanced bone formation and increased <jats:italic>osteocalcin (OCN)<\/jats:italic> and <jats:italic>osteopontin (OPN)<\/jats:italic> mRNA expression as well as activation of the BMP-Smad signaling pathway <jats:italic>in vivo<\/jats:italic>. In order to investigate the effect of a BMP-Smad signaling pathway, we injected mice with activated enzyme inhibitors (LDN-193189HCL) and subjected the mice to treadmill exercise intervention. LDN-193189HCL attenuated the BMD and bone mass mediated by medium-intensity exercise and BMP-Smad signaling pathway.<\/jats:p>","DOI":"10.3389\/fcell.2020.600639","type":"journal-article","created":{"date-parts":[[2020,11,24]],"date-time":"2020-11-24T05:59:21Z","timestamp":1606197561000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":19,"title":["Medium-Intensity Treadmill Exercise Exerts Beneficial Effects on Bone Modeling Through Bone Marrow Mesenchymal Stromal Cells"],"prefix":"10.3389","volume":"8","author":[{"given":"Lingli","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongguang","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le","family":"Lei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Zou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2020,11,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0113785","article-title":"Pdgf-aa promotes osteogenic differentiation and migration of mesenchymal stem cell by down-regulating pdgfr\u03b1 and derepressing bmp-smad1\/5\/8 signaling.","volume":"9","author":"Anna","year":"2014","journal-title":"PLoS One"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1357","DOI":"10.1590\/s0100-879x2006001000012","article-title":"Effect of treadmill gait on bone markers and bone mineral density of quadriplegic subjects.","volume":"39","author":"Carvalho","year":"2006","journal-title":"Braz. 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