破骨细胞通过响应其机械体内环境来适应其吸收活性而对骨重建至关重要。然而,这一过程的分子机制尚不清楚.这里,我们证明了抗酒石酸酸性磷酸酶(TRAP,Acp5),破骨细胞分泌的关键酶,骨重建和机械敏感性。使用CRISPR/Cas9报告小鼠,我们证明了骨细胞报告子(BCRIbsp/Acp5)小鼠具有荧光TRAP缺陷的破骨细胞,并检查了其在机械驱动的小梁骨重建过程中的活性。尽管BCRIbsp/Acp5小鼠在体外表现出小梁骨损伤和吸收能力降低,RNA测序显示关键破骨细胞相关基因如Ctsk的水平不变,Mmp9和Calcr。这些发现,与血清羧基末端胶原蛋白交联(CTX)和体内机械负荷结果共同表明体内破骨细胞的骨吸收能力未改变。此外,我们在BCRIbsp/Acp5和野生型(WT)小鼠的小梁骨重建过程中表现出相似的机械调节。因此,这项研究为骨重建和机械感觉背景下TRAP活动的动力学提供了有价值的见解。
Osteoclasts are essential for bone remodeling by adapting their resorptive activity in response to their mechanical in vivo environment. However, the molecular mechanisms underlying this process remain unclear. Here, we demonstrated the role of tartrate-resistant acid phosphatase (TRAP, Acp5), a key enzyme secreted by osteoclasts, in bone remodeling and
mechanosensitivity. Using CRISPR/Cas9 reporter mice, we demonstrated bone cell reporter (BCRIbsp/Acp5) mice feature fluorescent TRAP-deficient osteoclasts and examined their activity during mechanically driven trabecular bone remodeling. Although BCRIbsp/Acp5 mice exhibited trabecular bone impairments and reduced resorption capacity in vitro, RNA sequencing revealed unchanged levels of key osteoclast-associated genes such as Ctsk, Mmp9, and Calcr. These findings, in conjunction with serum carboxy-terminal collagen crosslinks (CTX) and in vivo mechanical loading outcomes collectively indicated an unaltered bone resorption capacity of osteoclasts in vivo. Furthermore, we demonstrated similar mechanoregulation during trabecular bone remodeling in BCRIbsp/Acp5 and wild-type (WT) mice. Hence, this study provides valuable insights into the dynamics of TRAP activity in the context of bone remodeling and mechanosensation.