Sost, encoding sclerostin, is an osteocyte-derived negative regulator of bone formation [1,4]. It inhibits the canonical Wnt signaling pathway, a key pathway in bone metabolism [1]. Sost is of great importance in maintaining bone homeostasis and skeletal integrity [2]. Genetic models, such as transgenic and knockout mice, have been crucial for studying Sost [1].

In mice with wear-particle-induced cranial osteolysis, SOST gene suppression stimulated osteocyte Wnt/β-catenin signaling, preventing bone resorption and attenuating particle-induced osteolysis. Blocking SOST also protected against bone loss and deformation caused by titanium particles [3]. In a glucocorticoid-associated osteonecrosis of the femoral head (GA-ONFH) rat model, SOST knockout ameliorated the incidence of osteonecrosis and improved bone metabolism. Sclerostin derived from osteocytes impaired osteogenesis and angiogenesis via inhibiting the Wnt pathway in GA-ONFH [2].

In conclusion, Sost plays a vital role in bone metabolism by regulating the Wnt signaling pathway. Studies using SOST knockout mouse models have provided insights into its role in diseases like particle-induced osteolysis and GA-ONFH, helping to understand the mechanisms of bone-related diseases and potentially guiding the development of new therapeutic strategies.

References:

1. Sebastian, Aimy, Loots, Gabriela G. 2017. Genetics of Sost/SOST in sclerosteosis and van Buchem disease animal models. In Metabolism: clinical and experimental, 80, 38-47. doi:10.1016/j.metabol.2017.10.005. https://pubmed.ncbi.nlm.nih.gov/29080811/

2. Huang, Junming, Ma, Tianle, Wang, Chenzhong, Jiang, Chang, Yan, Zuoqin. 2024. SOST/Sclerostin impairs the osteogenesis and angiogesis in glucocorticoid-associated osteonecrosis of femoral head. In Molecular medicine (Cambridge, Mass.), 30, 167. doi:10.1186/s10020-024-00933-5. https://pubmed.ncbi.nlm.nih.gov/39342093/

3. Jiao, Zixue, Chai, Hao, Wang, Shendong, Huang, Qun, Xu, Wei. 2023. SOST gene suppression stimulates osteocyte Wnt/β-catenin signaling to prevent bone resorption and attenuates particle-induced osteolysis. In Journal of molecular medicine (Berlin, Germany), 101, 607-620. doi:10.1007/s00109-023-02319-2. https://pubmed.ncbi.nlm.nih.gov/37121919/

4. van Bezooijen, Rutger L, ten Dijke, Peter, Papapoulos, Socrates E, Löwik, Clemens W G M. . SOST/sclerostin, an osteocyte-derived negative regulator of bone formation. In Cytokine & growth factor reviews, 16, 319-27. doi:. https://pubmed.ncbi.nlm.nih.gov/15869900/