Leptin accelerates the pathogenesis of heterotopic ossification in rat tendon tissues via mTORC1 signaling. Issue 2 (5th June 2017)

• Record Type: Journal Article
• Authors: Jiang, Huaji; Chen, Yuhui; Chen, Guorong; Tian, Xinggui; Tang, Jiajun; Luo, Lei; Huang, Minjun; Yan, Bin; Ao, Xiang; Zhou, Wen; Wang, Liping; Bai, Xiaochun; Zhang, Zhongmin; Wang, Liang; Xian, Cory J.
• Is Part Of: Journal of cellular physiology. Volume 233:Issue 2(2018:Feb.)
• Page Start: 1017
• Page End: 1028
• Publication Date: 2017-06-05
• Subjects: leptin -- tendon‐derived stem cells -- osteogenic differentiation; Physiology -- Periodicals; Cell physiology -- Periodicals; 571.6
• DOI: 10.1002/jcp.25955
• Languages: English
• ISSNs: 0021-9541

Abstract

Abstract : Leptin, an adipocyte‐derived cytokine associated with bone metabolism, is believed to play a critical role in the pathogenesis of heterotopic ossification (HO). The effect and underlying action mechanism of leptin were investigated on osteogenic differentiation of tendon‐derived stem cells (TDSCs) in vitro and the HO formation in rat tendons. Isolated rat TDSCs were treated with various concentrations of leptin in the presence or absence of mTORC1 signaling specific inhibitor rapamycin in vitro. A rat model with Achilles tenotomy was employed to evaluate the effect of leptin on HO formation together with or without rapamycin treatment. In vitro studies with TDSCs showed that leptin increased the expression of osteogenic biomarkers (alkaline phosphatase, runt‐related transcription factor 2, osterix, osteocalcin) and enhanced mineralization of TDSCs via activating the mTORC1 signal pathway (as indicated by phosphorylation of p70 ribosomal S6 kinase 1 and p70 ribosomal S6). However, mTORC1 signaling blockade with rapamycin treatment suppressed leptin‐induced osteogenic differentiation and mineralization. In vivo studies showed that leptin promoted HO formation in the Achilles tendon after tenotomy, and rapamycin treatment blocked leptin‐induced HO formation. In conclusion, leptin can promote TDSC osteogenic differentiation and heterotopic bone formation via mTORC1 signaling in both vitro and vivo model, which provides a new potential therapeutic target for HO prevention. Abstract : Leptin promotes the osteogenic differentiation of tendon‐derived stem cells (TDSCs) in heterotopic ossification (HO). mTORC1 signaling favors differentiation of TDSCs into osteoblasts and promotes expression of Runx2 and OSX in HO of Achilles tendon.