mTORC1型
软骨发生
细胞生物学
软骨内骨化
基因沉默
化学
TSC1
雷氏菌
PI3K/AKT/mTOR通路
信号转导
软骨
生物
间充质干细胞
解剖
生物化学
基因
作者
Jiaming Fu,Jie Zhang,Tao Jiang,Xiang Ao,Peng Li,Zhengnan Lian,Chenglong Li,Xibing Zhang,Jie Liu,Minjun Huang,Zhongmin Zhang,Liang Wang
出处
期刊:Bone
[Elsevier]
日期:2022-10-01
卷期号:163: 116507-116507
被引量:10
标识
DOI:10.1016/j.bone.2022.116507
摘要
Heterotopic ossification (HO) is a pathological bone formation based on endochondral ossification distinguished by ossification within muscles, tendons, or other soft tissues. There has been growing studies focusing on the treatment with rapamycin to inhibit HO, but the mechanism of mTORC1 on HO remains unclear. Tendon cells (TDs) are the first cells to form during tendon heterotopic ossification. Here, we used an in vivo model of HO and an in vitro model of chondrogenesis induction to elucidate the effect and underlying mechanism of mTORC1 in HO. The current study highlights the effect of rapamycin on murine Achilles tenotomy-induced HO and the role of mTORC1 signaling pathway on TDs. Our result showed that mTORC1 was activation in the early stage of HO, whereas the mTORC1 maintained low expression in the mature ectopic cartilage tissue and the ectopic bone formation sites. The use of mTORC1-specific inhibitor (rapamycin) immediately after Achilles tendon injury could suppress the formation of HO; once ectopic cartilage and bone had formed, treatment with rapamycin could not significantly inhibit the progression of HO. Mechanistically, mTORC1 stimulation by silencing of TSC1 promoted the expression of the chondrogenic markers in TDs. In TDs, treated with mTORC1 stimulation by silencing of TSC1, mTORC1 increased the activation of the NF-κB signaling pathway. NF-κB selective inhibitor BAY11-7082 significantly suppressed the chondrogenesis of TDs that treated with mTORC1 stimulation by silencing of TSC1. Together, our findings demonstrated that mTORC1 promoted HO by regulating TDs chondrogenesis partly through the NF-κB signaling pathway; and rapamycin could be a viable HO therapeutic regimen.
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