Osteocyte-Intrinsic TGF-β Signaling Regulates Bone Quality through Perilacunar/Canalicular Remodeling.
Osteocyte-Intrinsic TGF-β Signaling Regulates Bone Quality through Perilacunar/Canalicular Remodeling.
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DOI：
10.1016/j.celrep.2017.10.115
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发表时间：
2017-11-28
期刊：
影响因子：
8.8
通讯作者：
Alliston T
中科院分区：
文献类型：
--
作者：
Dole NS;Mazur CM;Acevedo C;Lopez JP;Monteiro DA;Fowler TW;Gludovatz B;Walsh F;Regan JN;Messina S;Evans DS;Lang TF;Zhang B;Ritchie RO;Mohammad KS;Alliston T
骨质量差导致糖尿病、衰老和骨生成障碍中的骨脆性。然而，控制骨质量的机制还不清楚，导致目前缺乏诊断或治疗骨质量缺陷的策略。TGFβ信号传导是已知的调节骨材料质量的关键机制，但其在该调节中的细胞靶点是未知的。研究表明骨细胞直接重塑其骨腔/骨小管周围基质，这使我们假设TGFβ通过骨腔/骨小管周围重塑（PLR）控制骨质量。使用抑制剂和TGFβ信号传导（TβRIIocy−/−）存在骨细胞内在缺陷的小鼠，我们表明TGFβ以细胞内在方式调节PLR以控制骨质量。总之，本研究强调骨细胞是通过PLR执行骨质量生物控制的关键，从而突出了骨细胞介导的骨内环境稳定和脆弱性中的骨细胞介导的骨泡/骨小管重塑的基本作用。
Poor bone quality contributes to bone fragility in diabetes, aging, and osteogenesis imperfecta. However, the mechanisms controlling bone quality are not well understood, contributing to the current lack of strategies to diagnose or treat bone quality deficits. TGFβ signaling is a crucial mechanism known to regulate the material quality of bone, but its cellular target in this regulation is unknown. Studies showing that osteocytes directly remodel their perilacunar/canalicular matrix led us to hypothesize that TGFβ controls bone quality through perilacunar/canalicular remodeling (PLR). Using inhibitors and mice with an osteocyte-intrinsic defect in TGFβ signaling (TβRIIocy−/−), we show that TGFβ regulates PLR in a cell-intrinsic manner to control bone quality. Altogether, this study emphasizes that osteocytes are key in executing the biological control of bone quality through PLR, thereby highlighting the fundamental role of osteocyte mediated perilacunar/canalicular remodeling in bone homeostasis and fragility.
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