Acvr1 deletion in osteoblasts impaired mandibular bone mass through compromised osteoblast differentiation and enhanced sRANKL-induced osteoclastogenesis.
Acvr1 deletion in osteoblasts impaired mandibular bone mass through compromised osteoblast differentiation and enhanced sRANKL-induced osteoclastogenesis.
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成骨细胞中 Acvr1 缺失会通过成骨细胞分化受损和 sRANKL 诱导的破骨细胞生成增强来损害下颌骨质量
DOI：
10.1002/jcp.30183
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发表时间：
2021-06
影响因子：
5.6
通讯作者：
Sun H
中科院分区：
文献类型：
--
作者：
Hu Y;Hao X;Liu C;Ren C;Wang S;Yan G;Meng Y;Mishina Y;Shi C;Sun H
骨形态发生蛋白（BMP）信号传导在骨稳态中是众所周知的。然而，BMP信号对下颌骨的生理作用在很大程度上是未知的，因为下颌骨具有与其他骨骼不同的功能和特征。在这项研究中，我们通过Osterix-Cre删除成骨细胞系细胞中BMP I型受体Acvr 1，研究了BMP信号传导在下颌骨骨稳态中的作用。我们发现条件性基因敲除小鼠在出生后第21天和第42天的下颌骨丢失呈年龄依赖性。骨量减少与成骨细胞分化受损以及破骨细胞生成增强有关，破骨细胞生成增强继发于体内成骨细胞的变化。体外研究发现，缺失Acvr 1的下颌骨骨髓基质细胞（BMSCs）成骨分化显着受损。当野生型骨髓巨噬细胞与缺乏Acvr 1的BMSCs直接或间接共培养时，与对照BMSCs共培养相比，破骨细胞的增殖和分化均被诱导，这通过多核细胞的增加来证明。此外，我们证明体外破骨细胞生成的增加至少部分是由于可溶性核因子-κB配体受体激活剂（sRANKL）的分泌，这可能是体内下颌骨丢失的原因。总体而言，我们的结果表明，ACVR 1通过成骨细胞分化和成骨细胞-破骨细胞通过sRANKL通讯在维持下颌骨稳态中发挥重要作用。
Bone morphogenetic protein (BMP) signaling is well known in bone homeostasis. However, the physiological effects of BMP signaling on mandibles are largely unknown, as the mandible has distinct functions and characteristics from other bones. In this study, we investigated the roles of BMP signaling in bone homeostasis of the mandibles by deleting BMP type I receptor Acvr1 in osteoblast lineage cells with Osterix‐Cre. We found mandibular bone loss in conditional knockout mice at the ages of postnatal day 21 and 42 in an age‐dependent manner. The decreased bone mass was related to compromised osteoblast differentiation together with enhanced osteoclastogenesis, which was secondary to the changes in osteoblasts in vivo. In vitro study revealed that deletion of Acvr1 in the mandibular bone marrow stromal cells (BMSCs) significantly compromised osteoblast differentiation. When wild type bone marrow macrophages were cocultured with BMSCs lacking Acvr1 both directly and indirectly, both proliferation and differentiation of osteoclasts were induced as evidenced by an increase of multinucleated cells, compared with cocultured with control BMSCs. Furthermore, we demonstrated that the increased osteoclastogenesis in vitro was at least partially due to the secretion of soluble receptor activator of nuclear factor‐κB ligand (sRANKL), which is probably the reason for the mandibular bone loss in vivo. Overall, our results proposed that ACVR1 played essential roles in maintaining mandibular bone homeostasis through osteoblast differentiation and osteoblast‐osteoclast communication via sRANKL.
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影响因子：
3.9
作者：
Pravitharangul, Anute;Suttapreyasri, Srisurang;Leethanakul, Chidchanok
通讯作者：
Leethanakul, Chidchanok
影响因子：
4.8
作者：
Ikeda, T;Kasai, M;Hirokawa, K
通讯作者：
Hirokawa, K
影响因子：
4.1
作者：
Akintoye, Sunday O.;Lam, Thanh;Robey, Pamela G.
通讯作者：
Robey, Pamela G.
影响因子：
0.5
作者：
Omi M;Mishina Y
通讯作者：
Mishina Y
DOI：
10.1359/jbmr.090806
发表时间：
2010-02
期刊：
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
影响因子：
--
作者：
Kamiya N;Kobayashi T;Mochida Y;Yu PB;Yamauchi M;Kronenberg HM;Mishina Y
通讯作者：
Mishina Y