Leptin Potentiates BMP9-Induced Osteogenic Differentiation of Mesenchymal Stem Cells Through the Activation of JAK/STAT Signaling.
Mesenchymal stem cells (MSCs) are multipotent progenitors that have the ability to differentiate into multiple lineages, including bone, cartilage, and fat. We previously demonstrated that the least known bone morphogenetic protein (BMP)9 (also known as growth differentiation factor 2) is one of the potent osteogenic factors that can induce both osteogenic and adipogenic differentiation of MSCs. Nonetheless, the molecular mechanism underlying BMP9 action remains to be fully understood. Leptin is an adipocyte-derived hormone in direct proportion to the amount of body fat, and exerts pleiotropic functions, such as regulating energy metabolism, bone mass, and mineral density. In this study, we investigate the potential effect of leptin signaling on BMP9-induced osteogenic differentiation of MSCs. We found that exogenous leptin potentiated BMP9-induced osteogenic differentiation of MSCs both in vitro and in vivo, while inhibiting BMP9-induced adipogenic differentiation. BMP9 was shown to induce the expression of leptin and leptin receptor in MSCs, while exogenous leptin upregulated BMP9 expression in less differentiated MSCs. Mechanistically, we demonstrated that a blockade of JAK signaling effectively blunted leptin-potentiated osteogenic differentiation induced by BMP9. Taken together, our results strongly suggest that leptin may potentiate BMP9-induced osteogenesis by cross-regulating BMP9 signaling through the JAK/STAT signaling pathway in MSCs. Thus, it is conceivable that a combined use of BMP9 and leptin may be explored as a novel approach to enhancing efficacious bone regeneration and fracture healing.
['Zhang|Bo|B|', 'Yang|Lijuan|L|', 'Zeng|Zongyue|Z|', 'Feng|Yixiao|Y|', 'Wang|Xi|X|', 'Wu|Xiaoxing|X|', 'Luo|Huaxiu|H|', 'Zhang|Jing|J|', 'Zhang|Meng|M|', 'Pakvasa|Mikhail|M|', 'Wagstaff|William|W|', 'He|Fang|F|', 'Mao|Yukun|Y|', 'Qin|Kevin|K|', 'Ding|Huimin|H|', 'Zhang|Yongtao|Y|', 'Niu|Changchun|C|', 'Wu|Meng|M|', 'Zhao|Xia|X|', 'Wang|Hao|H|', 'Huang|Linjuan|L|', 'Shi|Dayao|D|', 'Liu|Qing|Q|', 'Ni|Na|N|', 'Fu|Kai|K|', 'Athiviraham|Aravind|A|', 'Moriatis Wolf|Jennifer|J|', 'Lee|Michael J|MJ|', 'Hynes|Kelly|K|', 'Strelzow|Jason|J|', 'El Dafrawy|Mostafa|M|', 'Xia|Yayi|Y|', 'He|Tong-Chuan|TC|']
D050156:Adipogenesis D000818:Animals D001842:Bone and Bones D002454:Cell Differentiation D002460:Cell Line D055427:Growth Differentiation Factor 2 D006801:Humans D053612:Janus Kinases D020738:Leptin D059630:Mesenchymal Stem Cells D051379:Mice D008819:Mice, Nude D010012:Osteogenesis D050791:STAT Transcription Factors D015398:Signal Transduction D015854:Up-Regulation
leptin osteogenic differentiation mesenchymal stem cells BMP9 bone mass osteogenesis adipogenesis