اسکلروستین
| Sclerostin | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| شناسه‌ها | |||||||||
| نماد | Sclerostin | ||||||||
| پی‌فم | PF05463 | ||||||||
| اینترپرو | IPR008835 | ||||||||
| |||||||||
اسکلروستین (انگلیسی: Sclerostin) پروتئینی است که در انسان توسط ژن «SOST» کُد می‌شود[۴][۵] که بر روی بازوی بلند کروموزوم ۱۷ واقع است.[۶]
این مولکول، یک گلیکوپروتئین است که توسط سلول‌های استخوانی (اوستئوسیت‌ها) ترشح می‌شود و خواص ضدآنابولیک در جریان استخوان‌سازی دارد[۷] و با مهار «مسیر سیگنال‌دهی Wnt»,[۸][۹] موجب کاهش ساخت استخوان می‌شود.[۸]
این پروتئین علاوه بر اوستئوسیت‌ها، در برخی کندروسیتها هم بیان می‌شود و استخوان‌سازی را توسط سلول‌های استخوان‌ساز (استوئوبلاست‌ها) مهار می‌کند.[۱۰][۱۱][۱۲]
تولید اسکلروستین، توسط هورمون پاراتیروئید،[۱۲][۱۳] فشارهای مکانیکی بر روی استخوان[۱۴] (مثلاً ورزش) و برخی سیتوکینها نظیر «پروستاگلاندین E2»،[۱۵] «اونکوستاتین M»، «کاردیوتروپین-۱» و «فاکتور مهارکنندهٔ لوکمی» مهار می‌شود.[۱۶] بالعکس، تولید اسکلروستین توسط کلسی‌تونین تحریک و افزایش می‌یابد.[۱۷] در نتیجه، خودتنظیمیِ فعالیتِ سلول‌های استخوان‌ساز (استوئوبلاست‌ها) توسط یک سیستم فیدبک منفی کنترل می‌شود.[۱۸]
جهش در ژن تولیدکنندهٔ این پروتئین منجر به بروز «بیماری فان بوخم» و اسکلروستئوز می‌شود.[۶]
منابع[ویرایش]
- ↑ ۱٫۰ ۱٫۱ ۱٫۲ GRCm38: Ensembl release 89: ENSMUSG00000001494 - Ensembl, May 2017
- ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ↑ Brunkow ME, Gardner JC, Van Ness J, Paeper BW, Kovacevich BR, Proll S, Skonier JE, Zhao L, Sabo PJ, Fu Y, Alisch RS, Gillett L, Colbert T, Tacconi P, Galas D, Hamersma H, Beighton P, Mulligan J (Mar 2001). "Bone dysplasia sclerosteosis results from loss of the SOST gene product, a novel cystine knot-containing protein". American Journal of Human Genetics. 68 (3): 577–89. doi:10.1086/318811. PMC 1274471. PMID 11179006.
- ↑ Balemans W, Ebeling M, Patel N, Van Hul E, Olson P, Dioszegi M, Lacza C, Wuyts W, Van Den Ende J, Willems P, Paes-Alves AF, Hill S, Bueno M, Ramos FJ, Tacconi P, Dikkers FG, Stratakis C, Lindpaintner K, Vickery B, Foernzler D, Van Hul W (Mar 2001). "Increased bone density in sclerosteosis is due to the deficiency of a novel secreted protein (SOST)". Human Molecular Genetics. 10 (5): 537–43. doi:10.1093/hmg/10.5.537. PMID 11181578.
- ↑ ۶٫۰ ۶٫۱ Van Bezooijen, R. L.; Papapoulos, S. E.; Hamdy, N. A.; Ten Dijke, P.; Löwik, C. W. (2005). "Control of bone formation by osteocytes? Lessons from the rare skeletal disorders sclerosteosis and van Buchem disease". BoneKEy-Osteovision. 2 (12): 33–38. doi:10.1138/20050189.
- ↑ "Entrez Gene: SOST sclerosteosis".
- ↑ ۸٫۰ ۸٫۱ Li X, Zhang Y, Kang H, Liu W, Liu P, Zhang J, Harris SE, Wu D (May 2005). "Sclerostin binds to LRP5/6 and antagonizes canonical Wnt signaling". The Journal of Biological Chemistry. 280 (20): 19883–7. doi:10.1074/jbc.M413274200. PMID 15778503.
- ↑ Ellies DL, Viviano B, McCarthy J, Rey JP, Itasaki N, Saunders S, Krumlauf R (Nov 2006). "Bone density ligand, Sclerostin, directly interacts with LRP5 but not LRP5G171V to modulate Wnt activity". Journal of Bone and Mineral Research. 21 (11): 1738–49. doi:10.1359/jbmr.060810. PMID 17002572.
- ↑ Bonewald LF (Feb 2011). "The amazing osteocyte". Journal of Bone and Mineral Research. 26 (2): 229–38. doi:10.1002/jbmr.320. PMC 3179345. PMID 21254230.
- ↑ Burgers TA, Williams BO (Jun 2013). "Regulation of Wnt/β-catenin signaling within and from osteocytes". Bone. 54 (2): 244–9. doi:10.1016/j.bone.2013.02.022. PMC 3652284. PMID 23470835.
- ↑ ۱۲٫۰ ۱۲٫۱ Bellido T, Saini V, Pajevic PD (Jun 2013). "Effects of PTH on osteocyte function". Bone. 54 (2): 250–7. doi:10.1016/j.bone.2012.09.016. PMC 3552098. PMID 23017659.
- ↑ Bellido T, Ali AA, Gubrij I, Plotkin LI, Fu Q, O'Brien CA, Manolagas SC, Jilka RL (Nov 2005). "Chronic elevation of parathyroid hormone in mice reduces expression of sclerostin by osteocytes: a novel mechanism for hormonal control of osteoblastogenesis". Endocrinology. 146 (11): 4577–83. doi:10.1210/en.2005-0239. PMID 16081646.
- ↑ Robling AG, Niziolek PJ, Baldridge LA, Condon KW, Allen MR, Alam I, Mantila SM, Gluhak-Heinrich J, Bellido TM, Harris SE, Turner CH (Feb 2008). "Mechanical stimulation of bone in vivo reduces osteocyte expression of Sost/sclerostin". The Journal of Biological Chemistry. 283 (9): 5866–75. doi:10.1074/jbc.M705092200. PMID 18089564.
- ↑ Genetos DC, Yellowley CE, Loots GG (March 2011). "Prostaglandin E2 signals through PTGER2 to regulate sclerostin expression". PLOS ONE. 6 (3): e17772. doi:10.1371/journal.pone.0017772. PMC 3059227. PMID 21436889.
- ↑ Walker EC, McGregor NE, Poulton IJ, Solano M, Pompolo S, Fernandes TJ, Constable MJ, Nicholson GC, Zhang JG, Nicola NA, Gillespie MT, Martin TJ, Sims NA (Feb 2010). "Oncostatin M promotes bone formation independently of resorption when signaling through leukemia inhibitory factor receptor in mice". The Journal of Clinical Investigation. 120 (2): 582–92. doi:10.1172/JCI40568. PMC 2810087. PMID 20051625.
- ↑ Gooi JH, Pompolo S, Karsdal MA, Kulkarni NH, Kalajzic I, McAhren SH, Han B, Onyia JE, Ho PW, Gillespie MT, Walsh NC, Chia LY, Quinn JM, Martin TJ, Sims NA (Jun 2010). "Calcitonin impairs the anabolic effect of PTH in young rats and stimulates expression of sclerostin by osteocytes". Bone. 46 (6): 1486–97. doi:10.1016/j.bone.2010.02.018. PMID 20188226.
- ↑ http://users.telenet.be/zeldzame.ziekten/List.o/Pmenoposteo.htm
- مشارکت‌کنندگان ویکی‌پدیا. «Sclerostin». در دانشنامهٔ ویکی‌پدیای انگلیسی، بازبینی‌شده در ۲ ژانویه ۲۰۱۸.
برای مطالعهٔ بیشتر[ویرایش]
- Balemans W, Van Hul W (2007). "Human genetics of SOST". Journal of Musculoskeletal & Neuronal Interactions. 6 (4): 355–6. PMID 17185822.
- Balemans W, Patel N, Ebeling M, Van Hul E, Wuyts W, Lacza C, Dioszegi M, Dikkers FG, Hildering P, Willems PJ, Verheij JB, Lindpaintner K, Vickery B, Foernzler D, Van Hul W (Feb 2002). "Identification of a 52 kb deletion downstream of the SOST gene in patients with van Buchem disease". Journal of Medical Genetics. 39 (2): 91–7. doi:10.1136/jmg.39.2.91. PMC 1735035. PMID 11836356.
- Staehling-Hampton K, Proll S, Paeper BW, Zhao L, Charmley P, Brown A, Gardner JC, Galas D, Schatzman RC, Beighton P, Papapoulos S, Hamersma H, Brunkow ME (Jun 2002). "A 52-kb deletion in the SOST-MEOX1 intergenic region on 17q12-q21 is associated with van Buchem disease in the Dutch population". American Journal of Medical Genetics. 110 (2): 144–52. doi:10.1002/ajmg.10401. PMID 12116252.
- Balemans W, Foernzler D, Parsons C, Ebeling M, Thompson A, Reid DM, Lindpaintner K, Ralston SH, Van Hul W (Oct 2002). "Lack of association between the SOST gene and bone mineral density in perimenopausal women: analysis of five polymorphisms". Bone. 31 (4): 515–9. doi:10.1016/S8756-3282(02)00844-X. PMID 12398949.
- Clark HF, Gurney AL, Abaya E, Baker K, Baldwin D, Brush J, Chen J, Chow B, Chui C, Crowley C, Currell B, Deuel B, Dowd P, Eaton D, Foster J, Grimaldi C, Gu Q, Hass PE, Heldens S, Huang A, Kim HS, Klimowski L, Jin Y, Johnson S, Lee J, Lewis L, Liao D, Mark M, Robbie E, Sanchez C, Schoenfeld J, Seshagiri S, Simmons L, Singh J, Smith V, Stinson J, Vagts A, Vandlen R, Watanabe C, Wieand D, Woods K, Xie MH, Yansura D, Yi S, Yu G, Yuan J, Zhang M, Zhang Z, Goddard A, Wood WI, Godowski P, Gray A (Oct 2003). "The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment". Genome Research. 13 (10): 2265–70. doi:10.1101/gr.1293003. PMC 403697. PMID 12975309.
- Sevetson B, Taylor S, Pan Y (Apr 2004). "Cbfa1/RUNX2 directs specific expression of the sclerosteosis gene (SOST)". The Journal of Biological Chemistry. 279 (14): 13849–58. doi:10.1074/jbc.M306249200. PMID 14739291.
- van Bezooijen RL, Roelen BA, Visser A, van der Wee-Pals L, de Wilt E, Karperien M, Hamersma H, Papapoulos SE, ten Dijke P, Löwik CW (Mar 2004). "Sclerostin is an osteocyte-expressed negative regulator of bone formation, but not a classical BMP antagonist". The Journal of Experimental Medicine. 199 (6): 805–14. doi:10.1084/jem.20031454. PMC 2212719. PMID 15024046.
- Winkler DG, Yu C, Geoghegan JC, Ojala EW, Skonier JE, Shpektor D, Sutherland MK, Latham JA (Aug 2004). "Noggin and sclerostin bone morphogenetic protein antagonists form a mutually inhibitory complex". The Journal of Biological Chemistry. 279 (35): 36293–8. doi:10.1074/jbc.M400521200. PMID 15199066.
- Zhang Z, Henzel WJ (Oct 2004). "Signal peptide prediction based on analysis of experimentally verified cleavage sites". Protein Science. 13 (10): 2819–24. doi:10.1110/ps.04682504. PMC 2286551. PMID 15340161.
- Sutherland MK, Geoghegan JC, Yu C, Turcott E, Skonier JE, Winkler DG, Latham JA (Oct 2004). "Sclerostin promotes the apoptosis of human osteoblastic cells: a novel regulation of bone formation". Bone. 35 (4): 828–35. doi:10.1016/j.bone.2004.05.023. PMID 15454089.
- Uitterlinden AG, Arp PP, Paeper BW, Charmley P, Proll S, Rivadeneira F, Fang Y, van Meurs JB, Britschgi TB, Latham JA, Schatzman RC, Pols HA, Brunkow ME (Dec 2004). "Polymorphisms in the sclerosteosis/van Buchem disease gene (SOST) region are associated with bone-mineral density in elderly whites". American Journal of Human Genetics. 75 (6): 1032–45. doi:10.1086/426458. PMC 1182139. PMID 15514891.
- Winkler DG, Sutherland MS, Ojala E, Turcott E, Geoghegan JC, Shpektor D, Skonier JE, Yu C, Latham JA (Jan 2005). "Sclerostin inhibition of Wnt-3a-induced C3H10T1/2 cell differentiation is indirect and mediated by bone morphogenetic proteins". The Journal of Biological Chemistry. 280 (4): 2498–502. doi:10.1074/jbc.M400524200. PMID 15545262.
- Poole KE, van Bezooijen RL, Loveridge N, Hamersma H, Papapoulos SE, Löwik CW, Reeve J (Nov 2005). "Sclerostin is a delayed secreted product of osteocytes that inhibits bone formation". FASEB Journal. 19 (13): 1842–4. doi:10.1096/fj.05-4221fje. PMID 16123173.
- Gardner JC, van Bezooijen RL, Mervis B, Hamdy NA, Löwik CW, Hamersma H, Beighton P, Papapoulos SE (Dec 2005). "Bone mineral density in sclerosteosis; affected individuals and gene carriers". The Journal of Clinical Endocrinology and Metabolism. 90 (12): 6392–5. doi:10.1210/jc.2005-1235. PMID 16189254.