Inhibition of Axinl in osteoblast precursor cells leads to defects in postnatal bone growth through suppressing osteoclast formation
Inhibition of Axinl in osteoblast precursor cells leads to defects in postnatal bone growth through suppressing osteoclast formation
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成骨细胞前体细胞中 Axinl 的抑制通过抑制破骨细胞形成导致出生后骨生长缺陷
DOI：
10.1038/s41413-020-0104-5
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发表时间：
2020
期刊：
影响因子：
12.7
通讯作者：
Chen Di
中科院分区：
文献类型：
--
作者：
Shu Bing;Zhao Yongjian;Zhao Shitian;Pan Haobo;Xie Rong;Yi Dan;Lu Ke;Yang Junjie;Xue Chunchun;Huang Jian;Wang Jing;Zhao Dongfeng;Xiao Guozhi;Wang Yongjun;Chen Di
Axin1是β-catenin信号的负调节因子，其在成骨前体细胞中的作用尚不清楚。在本研究中，我们通过缺失成骨前体细胞中的Axinl来测定出生后骨生长的变化，并对新生和出生后Axin1~（Osx）小鼠的骨生长进行了分析，发现Axin1~(Osx) KO小鼠的增生性软骨面积大量扩大。Axin1~(Osx) KO小鼠骨髓腔内有大量软骨细胞和未吸收的软骨基质。Axin1~(Osx) KO小鼠干骺端和软骨下骨区破骨细胞形成明显减少，表现为trap阳性细胞数量减少，与MMP9-和cathepsin k阳性细胞数量减少有关。Axin1~(Osx) KO小鼠成骨细胞中OPG表达及OPG / Rankl比值显著升高。用Axinl~（Osx）小鼠成骨细胞条件培养基（CM）培养原代骨髓源性微噬细胞（BMM）后，其破骨细胞形成明显低于用WT小鼠条件培养基培养的BMM细胞。因此，成骨前体细胞中Axinl的缺失导致OPG增加，破骨细胞形成减少，导致出生后Axin1OSx KO小鼠骨生长延迟。
Axin1 is a negative regulator of β-catenin signaling and its role in osteoblast precursor cells remains undefined. In the present studies, we determined changes in postnatal bone growth by deletion of Axinl in osteoblast precursor cells and analyzed bone growth in newborn and postnatal Axin1~(Osx) mice and found that hypertrophic cartilage area was largely expanded in Axin1~(Osx) KO mice. A larger number of chondrocytes and unabsorbed cartilage matrix were found in the bone marrow cavity of Axin1~(Osx) KO mice. Osteoclast formation in metaphyseal and subchondral bone areas was significantly decreased, demonstrated by decreased TRAP-positive cell numbers, associated with reduction of MMP9- and cathepsin K-positive cell numbers in Axin1~(Osx) KO mice. OPG expression and the ratio of Opg to Rankl were significantly increased in osteoblasts of Axin1~(Osx) KO mice. Osteoclast formation in primary bone marrow derived microphage (BMM) cells was significantly decreased when BMM cells were cultured with conditioned media (CM) collected from osteoblasts derived from Axinl~(Osx) mice compared with BMM cells cultured with CM derived from WT mice. Thus, the loss of Axinl in osteoblast precursor cells caused increased OPG and the decrease in osteoclast formation, leading to delayed bone growth in postnatal Axin1OSx KO mice.