Sost, also known as sclerostin, is an osteocyte-derived negative regulator of bone formation. It inhibits bone formation mainly by suppressing the canonical Wnt signaling pathway [2,4]. Sost is highly relevant to bone homeostasis and skeletal integrity, making it an attractive target for treating metabolic bone diseases like osteoporosis [1].

In sclerosteosis patients, loss-of-function mutations in the SOST gene lead to osteoblast hyperactivity and progressive bone overgrowth, highlighting Sost's role in normal bone metabolism regulation [2]. In a cranial osteolysis mouse model, SOST inhibition activated the osteocyte Wnt/β-catenin signaling cascade, preventing wear particle-induced osteoclastogenesis and reducing periprosthetic osteolysis, indicating its importance in maintaining bone balance [5]. In a GA-ONFH rat model, SOST knockout ameliorated the incidence of osteonecrosis and improved bone metabolism, suggesting Sost impairs osteogenesis and angiogenesis in this disease [3].

In conclusion, Sost is a key regulator in bone formation and homeostasis. Gene knockout models, especially in mice, have revealed its crucial role in various bone-related disease conditions such as sclerosteosis, glucocorticoid-associated osteonecrosis of the femoral head, and particle-induced osteolysis. Understanding Sost's function through these models provides potential therapeutic strategies for treating bone-related disorders.