運動通過STAT3促進成骨來維持骨穩態

2023年4月2日，上海交通大學醫學院附屬上海第九人民醫院口腔頜面外科顱面正畸中心;上海交通大學口腔醫學院;國家口腔醫學中心;國家口腔疾病臨床研究中心;上海市口腔醫學重點實驗室;

上海市口腔醫學研究所。上海交通大學醫學院附屬第九人民醫院第二牙科中心;上海交通大學口腔醫學院;國家口腔醫學中心;國家口腔疾病臨床研究中心;

上海市口腔醫學重點實驗室;上海市口腔醫學研究所。)Center of Craniofacial Orthodontics, Department of Oral and Cranio-maxillofacial Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases;Shanghai Key Laboratory of Stomatology; Shanghai Research Institute of Stomatology.The 2nd Dental Center, Ninth People's Hospital,

Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University;

National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology;

Shanghai Research Institute of Stomatology.） Lingyong Jiang研究團隊在《International Journal of Biological Sciences》上發表論文，標題為：“Exercise maintains bone homeostasis by promoting osteogenesis through STAT3”

“運動通過STAT3促進成骨來維持骨穩態”

Abstract

Bone exhibits changes in density, strength, and microarchitecture in relation to mechanical loading mediated by exercise. Appropriate exercise maintains bone homeostasis, while the absence of exercise leads to disuse bone loss. However, the acting mechanism of mechanotransduction in bone remains unclear. We performed the running-wheel exercise and tail suspension model to study the effects of exercise on bone metabolism, and found that osteoblastic Signal transducer and activator of transcription 3 (STAT3) activity was closely related to exercise-induced bone mass and metabolism changes. With the Flexcell tension-loading system in vitro, mechanical force promoted STAT3 activity, which was accompanied by increased osteoblastic differentiation of the bone marrow mesenchymal stem cells (BMSCs). In contrast, the inhibition of STAT3 phosphorylation blocked force-induced osteoblastic differentiation. Furthermore, pharmacological inactivation of STAT3 impaired the increase in exercise-induced bone mass and osteogenesis. With an inducible conditional deletion mouse model, we found that the osteoblast lineage-specific Stat3 deletion could also block force-induced osteoblastic differentiation in vitro and impair exercise-promoted bone mass and osteogenesis in vivo. This confirmed the crucial role of osteoblastic STAT3 in exercise-mediated bone metabolism. Finally, colivelin, a STAT3 agonist, promoted osteoblastic differentiation in vitro and partly rescued exercise loss-induced disuse bone loss by improving osteogenesis in the tail suspension model. Taken together, our study revealed the essential role of STAT3 in maintaining exercise-mediated bone homeostasis. In addition, STAT3 might act as a potential target for osteoporosis caused by exercise loss.

摘要

在運動介導的機械負荷下，骨表現出密度、強度和微結構的變化。適當的運動可以維持骨穩態，而缺乏運動則會導致廢用性骨質流失。然而，骨力學轉導的作用機制尚不清楚。我們通過跑輪運動和懸尾模型研究運動對骨代謝的影響，發現成骨細胞信號轉導因子和轉錄激活因子3 (STAT3)活性與運動誘導的骨量和代謝變化密切相關。在Flexcell體外張力加載系統中，機械力促進STAT3活性，并伴隨著骨髓間充質干細胞(BMSCs)成骨分化的增加。相反，抑制STAT3磷酸化可阻斷力誘導的成骨細胞分化。此外，STAT3的藥理學失活損害了運動誘導的骨量和成骨的增加。通過誘導條件缺失小鼠模型，我們發現成骨細胞譜系特異性Stat3缺失也可以在體外阻斷力誘導的成骨細胞分化，并損害運動促進的骨量和體內成骨。這證實了成骨細胞STAT3在運動介導的骨代謝中的關鍵作用。最后，STAT3激動劑colivelin在體外促進成骨細胞分化，并通過改善尾部懸浮模型的成骨，部分挽救運動損失引起的廢用性骨損失。綜上所述，我們的研究揭示了STAT3在維持運動介導的骨穩態中的重要作用。此外，STAT3可能作為運動損失引起的骨質疏松癥的潛在靶點。

該論文中，BMSCs（骨髓間充質干細胞）體外培養是使用Ausbian特級胎牛血清完成的。欲了解或購買Ausbian特級胎牛血清可以聯系北京締一生物400-166-8600.