Reduction of SOST gene promotes bone formation through the Wnt/β‐catenin signalling pathway and compensates particle‐induced osteolysis
Reduction of SOST gene promotes bone formation through the Wnt/β‐catenin signalling pathway and compensates particle‐induced osteolysis
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SOST 基因的减少通过 Wnt/β-catenin 信号通路促进骨形成并补偿颗粒诱导的骨溶解
DOI：
10.1111/jcmm.15084
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发表时间：
2020-03
影响因子：
5.3
通讯作者：
徐炜
中科院分区：
文献类型：
--
作者：
张载航;郏新宇;方菁嶷;柴灏;黄群;佘昶;贾鹏;耿德春;徐炜
The increase in bone resorption and/or the inhibition of bone regeneration caused by wear particles are the main causes of periprosthetic osteolysis. The SOST gene and Sclerostin, a protein synthesized by the SOST gene, are the characteristic marker of osteocytes and regulate bone formation and resorption. We aimed to verify whether the SOST gene was involved in osteolysis induced by titanium (Ti) particles and to investigate the effects of SOST reduction on osteolysis. The results showed osteolysis on the skull surface with an increase of sclerostin levels after treated with Ti particles. Similarly, sclerostin expression in MLO‐Y4 osteocytes increased when treated with Ti particles in vitro. After reduction of SOST, local bone mineral density and bone volume increased, while number of lytic pores on the skull surface decreased and the erodibility of the skull surface was compensated. Histological analyses revealed that SOST reduction increased significantly alkaline phosphatase‐ (ALP) and osterix‐positive expression on the skull surface which promoted bone formation. ALP activity and mineralization of MC3T3‐E1 cells also increased in vitro when SOST was silenced, even if treated with Ti particles. In addition, Ti particles decreased β‐catenin expression with an increase in sclerostin levels, in vivo and in vitro. Inversely, reduction of SOST expression increased β‐catenin expression. In summary, our results suggested that reduction of SOST gene can activate the Wnt/β‐catenin signalling pathway, promoting bone formation and compensated for bone loss induced by Ti particles. Thus, this study provided new perspectives in understanding the mechanisms of periprosthetic osteolysis.
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影响因子：
4.1
作者：
Kanaji, Arihiko;Caicedo, Marco S.;Virdi, Amarjit S.;Sumner, D. Rick;Hallab, Nadim J.;Sena, Kotaro
通讯作者：
Sena, Kotaro
影响因子：
3.7
作者：
Leong, Wai Fook;Zhou, Tielin;Lim, Gek Liang;Li, Baojie
通讯作者：
Li, Baojie
DOI：
10.1016/j.bbadis.2018.07.034
发表时间：
2018-10
期刊：
Biochimica et biophysica acta. Molecular basis of disease
影响因子：
--
作者：
Li F;Cain JD;Tombran-Tink J;Niyibizi C
通讯作者：
Niyibizi C
影响因子：
3.7
作者：
Wijenayaka AR;Kogawa M;Lim HP;Bonewald LF;Findlay DM;Atkins GJ
通讯作者：
Atkins GJ
DOI：
--
发表时间：
2009
期刊：
Bulletin of the NYU hospital for joint diseases
影响因子：
--
作者：
N. Hallab;J. Jacobs
通讯作者：
N. Hallab;J. Jacobs