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Sclerostin is a protein that in humans is encoded by the SOST gene.
Sclerostin is a secreted glycoprotein with a C-terminal cysteine knot-like (CTCK) domain and sequence similarity to the DAN (differential screening-selected gene aberrative in neuroblastoma) family of bone morphogenetic protein (BMP) antagonists. Sclerostin is produced by the osteocyte and has anti-anabolic effects on bone formation
|Record ID: 1515564825||From: 台灣|
Sclerostin, the product of the SOST gene, located on chromosome 17q12–q21 in humans, was originally believed to be a non-classical bone morphogenetic protein (BMP) antagonist. More recently sclerostin has been identified as binding to LRP5/6 receptors and inhibiting the Wnt signaling pathway. The inhibition of the Wnt pathway leads to decreased bone formation. Although the underlying mechanisms are unclear, it is believed that the antagonism of BMP-induced bone formation by sclerostin is mediated by Wnt signaling, but not BMP signaling pathways. Sclerostin is expressed in osteocytes and some chondrocytes and it inhibits bone formation by osteoblasts.
Sclerostin production by osteocytes is inhibited by parathyroid hormone, mechanical loading and cytokines including prostaglandin E2, oncostatin M, cardiotrophin-1 and leukemia inhibitory factor. Sclerostin production is increased by calcitonin. Thus, osteoblast activity is self regulated by a negative feedback system
|Record ID: 1515564825R001||From: 台灣|
Mutations in the gene that encodes the sclerostin protein are associated with disorders associated with high bone mass, sclerosteosis and van Buchem disease.
van Buchem disease is also an autosomal recessive skeletal disease characterized by bone overgrowth. It was first described in 1955 as "hyperostosis corticalis generalisata familiaris", but was given the current name in 1968. Excessive bone formation is most prominent in the skull, mandible, clavicle, ribs and diaphyses of long bones and bone formation occurs throughout life. It is a very rare condition with about 30 known cases in 2002. In 1967 van Buchem characterized the disease in 15 patients of Dutch origin. Patients with sclerosteosis are distinguished from those with van Buchem disease because they are often taller and have hand malformations.
An antibody for sclerostin is being developed because of the protein’s specificity to bone. Its use has increased bone growth in preclinical trials in osteoporotic rats and monkeys. In a Phase I study, a single dose of anti-sclerostin antibody from Amgen (Romosozumab) increased bone density in the hip and spine in healthy men and postmenopausal women and the drug was well tolerated. In a Phase II trial, one year of the antibody treatment in osteoporotic women increased bone density more than bisphosphonate and teriparatide treatment; it had mild injection side effects. A Phase II trial of a monoclonal human antibody to sclerostin from Eli Lilly had positive effects on post-menopausal women. Monthly treatments of the antibody for one year increased the bone mineral density of the spine and hip by 18 percent and 6 percent, respectively, compared to the placebo group. In a Phase III trial, one year of Romosozumab treatment in post-menopausal women reduced the risk of vertebral fractures compared to the placebo group. It also increased the bone mineral density in the lumbar spine (13.3% versus 0.0%), femoral neck (5.2% versus -0.7%) and total hip (6.8% versus 0.0%) compared to the placebo group. Adverse events were balanced between the groups.
The Amgen drug is expected to be on the market in 2017. In addition, OsteoGeneX is developing small molecule inhibitors of sclerostin.
|Record ID: 1515564825R002||From: 台灣|
|自由車選手如果玩全沒有步行運動輔助 可能骨疏鬆 老人要防骨疏鬆骨折 致死率高
反之 有罕見疾病硬結性骨化症KEGG DISEASE硬結性骨化症（sclerosteosis）．SOST遺伝子コード領域の不活性型変異による，骨密度の増加を特徴とする疾患である．類似疾患であるvan Buchem病では，SOST遺伝子下流に52 kbpの欠失が存在し，SOST発現の低下から骨量の増加が惹起されるものと考えられている．
|Record ID: 1515564825R003||From: 台灣|
|骨鈣蛋白，也被稱為骨含伽馬羧酸蛋白，是一種非膠原蛋白質，可見於骨或牙本質之中。因其含 伽馬羧酸基團, 所以其合成是維生素K依賴性的。在人體，骨鈣蛋白是由BGLAP 基因編碼的。 維基百科
Osteocalcin - Wikipedia
Osteocalcin, also known as bone gamma-carboxyglutamic acid-containing protein (BGLAP), is a noncollagenous protein hormone found in bone and dentin. Because it has gla domains, its synthesis is vitamin K dependent. In humans, the osteocalcin is encoded by the BGLAP gene. Its receptor is GPRC6A.
|Record ID: 1515564825R004||From: 台灣|
|骨鈣蛋白僅由成骨細胞分泌，它在人體代謝調節方面有一定作用， 並具有「促成骨」作用。 它也涉及骨礦化和鈣離子動態平衡。 骨鈣蛋白在人體內也是一種荷爾蒙，它可促使胰腺的beta細胞釋放更多的胰島素, 並同時指示脂肪細胞 釋放荷爾蒙脂聯素來提高對胰島素的敏感性。
當前的數據暗示骨鈣蛋白在男性生育能力方面扮演的一種可能的角色。 來自哥倫比亞大學醫學中心的研究提出骨鈣蛋白可能增強睪酮的分泌。 雖然這些研究只由單獨的一家實驗室進行，但至少有其它兩個團體曾獨立確認了骨鈣蛋白在胰島素分泌方面的作用。
|Record ID: 1515564825R005||From: 台灣|
|Record ID: 1515564825R006||From: 台灣|