TRPV1 deletion impaired fracture healing and inhibited osteoclast and osteoblast differentiation.
TRPV1 deletion impaired fracture healing and inhibited osteoclast and osteoblast differentiation.
复制标题
TRPV1 缺失损害骨折愈合并抑制破骨细胞和成骨细胞分化
DOI：
10.1038/srep42385
复制
发表时间：
2017-02-22
影响因子：
4.6
通讯作者：
Zhang Y
中科院分区：
文献类型：
--
作者：
He LH;Liu M;He Y;Xiao E;Zhao L;Zhang T;Yang HQ;Zhang Y
破骨细胞和成骨细胞在骨折愈合过程中起着重要作用，引起了临床的广泛关注。破骨细胞缺乏或成骨细胞活性降低会损害骨折愈合。TRPV 1是Ca 2+渗透性阳离子通道亚家族的成员，TRPV 1的药理学抑制可防止卵巢切除术诱导的骨丢失，这使得TRPV 1成为骨质疏松症的潜在靶点。然而，长期抑制TRPV 1或TRPV 1缺失是否会影响骨折愈合过程尚不清楚。在这项研究中，我们发现，野生型小鼠表现出良好的重塑骨折骨痂，而TRPV 1基因敲除小鼠仍然有一个明显的骨折间隙与未吸收的软骨痂骨折后4周。TRPV 1基因敲除的骨折骨痂中破骨细胞数量减少，破骨细胞的形成和吸收活性在体外也受到损害。TRPV 1缺失降低破骨细胞前体的钙振荡频率和峰值细胞质浓度，随后减少NFATc 1的表达和核转位，下调DC-stamp、组织蛋白酶K和ATP 6V。此外，TRPV 1基因缺失可导致骨髓基质细胞（BMSCs）中Runx 2和ALP的mRNA和蛋白表达降低，并减少钙沉积。我们的研究结果表明，TRPV 1缺失损害骨折愈合，并抑制破骨细胞和骨生成。
Fracture healing, in which osteoclasts and osteoblasts play important roles, has drawn much clinical attention. Osteoclast deficiency or decreased osteoblast activity will impair fracture healing. TRPV1 is a member of the Ca2+permeable cation channel subfamily, and pharmacological inhibition of TRPV1 prevents ovariectomy-induced bone loss, which makes TRPV1 a potential target for osteoporosis. However, whether long term TRPV1 inhibition or TRPV1 deletion will affect the fracture healing process is unclear. In this study, we found that the wild-type mice showed a well-remodeled fracture callus, whereas TRPV1 knockout mice still had an obvious fracture gap with unresorbed soft-callus 4 weeks post-fracture. The number of osteoclasts was reduced in the TRPV1 knockout fracture callus, and osteoclast formation and resorption activity were also impairedin vitro. TRPV1 deletion decreased the calcium oscillation frequency and peak cytoplasmic concentration in osteoclast precursors, subsequently reducing the expression and nuclear translocation of NFATc1 and downregulating DC-stamp, cathepsin K, and ATP6V. In addition, TRPV1 deletion caused reduced mRNA and protein expression of Runx2 and ALP in bone marrow stromal cells (BMSCs) and reduced calcium depositionin vitro. Our results suggest that TRPV1 deletion impairs fracture healing, and inhibited osteoclastogenesis and osteogenesis.