Sost, also known as the gene encoding sclerostin, is an osteocyte-derived negative regulator of bone formation. It functions by inhibiting the canonical Wnt signaling pathway and BMP-stimulated bone formation, playing a crucial role in bone homeostasis [1,3,5].

In sclerosteosis and van Buchem disease animal models, loss-of-function mutations in the SOST gene or a noncoding deletion affecting its regulation lead to osteoblast hyperactivity and progressive bone overgrowth, highlighting its role in normal bone metabolism regulation [1]. In glucocorticoid-associated osteonecrosis of the femoral head (GA-ONFH) rat model, SOST knockout ameliorated the incidence of osteonecrosis and improved bone metabolism, as sclerostin from osteocytes impairs osteogenesis and angiogenesis via inhibiting the Wnt pathway [2]. Also, in a cranial osteolysis mouse model, SOST inhibition triggered the osteocyte Wnt/β -catenin signaling cascade and prevented wear particle-induced osteoclastogenesis, reducing periprosthetic osteolysis [4].

In conclusion, Sost is essential for maintaining bone homeostasis by negatively regulating bone formation through the Wnt signaling pathway. Gene knockout mouse models have revealed its significance in diseases such as sclerosteosis, van Buchem disease, GA-ONFH, and periprosthetic osteolysis, providing insights into potential therapeutic strategies for these bone-related conditions.

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. 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/

4. 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/

5. Qin, Long-Juan, Ding, Da-Xia, Cui, Lu-Lu, Huang, Qing-Yang. . [Expression and regulation of the SOST gene]. In Yi chuan = Hereditas, 35, 939-47. doi:. https://pubmed.ncbi.nlm.nih.gov/23956082/