Sclerostin is a locally acting regulator of late-osteoblast/preosteocyte differentiation and regulates mineralization through a MEPE-ASARM-dependent mechanism

Journal of Bone and Mineral Research

Volumn 26, Issue 7, 2011, Pages 1425-1436

  Atkins, Gerald J ^a   Rowe, Peter S ^b   Lim, Hui P ^a   Welldon, Katie J ^a   Ormsby, Renee ^a   Wijenayaka, Asiri R ^a   Zelenchuk, Lesya ^b   Evdokiou, Andreas ^a   Findlay, David M ^a  

^a UNIVERSITY OF ADELAIDE   (Australia)

^b UNIVERSITY OF KANSAS SCHOOL OF MEDICINE   (United States)

Author keywords

ASARM; MEPE; Osteocyte; Sclerostin; Sost

Indexed keywords

ACIDIC SERINE ASPARTATE RICH MEPE PROTEIN; MATRIX EXTRACELLULAR PHOSPHOGLYCOPROTEIN; MESSENGER RNA; RECOMBINANT HUMAN SCLEROSTIN; SCLEROSTIN; UNCLASSIFIED DRUG;

ADULT; ANIMAL TISSUE; ARTICLE; BONE MASS; BONE MINERALIZATION; CELL DIFFERENTIATION; CELL TYPE; CONCENTRATION RESPONSE; CONTROLLED STUDY; GENE EXPRESSION; HUMAN; HUMAN TISSUE; IMMUNOHISTOCHEMISTRY; MALE; MOUSE; NONHUMAN; OSTEOBLAST; OSTEOCYTE; PROTEIN DOMAIN; PROTEIN LOCALIZATION; PROTEIN MOTIF; REGULATORY MECHANISM;

ANIMALS; ANTIBODIES, NEUTRALIZING; BONE MORPHOGENETIC PROTEINS; CALCIFICATION, PHYSIOLOGIC; CELL DIFFERENTIATION; CELLS, CULTURED; EXTRACELLULAR MATRIX PROTEINS; GENE EXPRESSION REGULATION; GENETIC MARKERS; GLYCOPROTEINS; HUMANS; HYPOPHOSPHATEMIA; MICE; MODELS, BIOLOGICAL; OSTEOBLASTS; OSTEOCYTES; PHEX PHOSPHATE REGULATING NEUTRAL ENDOPEPTIDASE; PHOSPHOPROTEINS; RECOMBINANT PROTEINS;

EID: 79954637641     PISSN: 08840431     EISSN: 15234681     Source Type: Journal    
DOI: 10.1002/jbmr.345     Document Type: Article

References (67)

1. Baron R, Rawadi G, Roman-Roman S,. Wnt signaling: a key regulator of bone mass. Curr Top Dev Biol. 2006; 76: 103-127. (Pubitemid 44760540)
2. Li X, Ominsky MS, Niu QT, et al. Targeted deletion of the sclerostin gene in mice results in increased bone formation and bone strength. J Bone Miner Res. 2008; 23: 860-869. (Pubitemid 351768804)
3. ten Dijke P, Krause C, de Gorter DJ, Lowik CW, van Bezooijen RL,. Osteocyte-derived sclerostin inhibits bone formation: its role in bone morphogenetic protein and Wnt signaling. J Bone Joint Surg Am. 2008; 90: S31-35.
4. Balemans W, Patel N, Ebeling M, et al. Identification of a 52-kb deletion downstream of the SOST gene in patients with van Buchem disease. J Med Genet. 2002; 39: 91-97. (Pubitemid 34146376)
5. Staehling-Hampton K, Proll S, Paeper BW, et al. A 52-kb deletion in the SOST-MEOX1 intergenic region on 17q12-q21 is associated with van Buchem disease in the Dutch population. Am J Med Genet. 2002; 110: 144-152.
6. Li X, Ominsky MS, Warmington KS, et al. Sclerostin antibody treatment increases bone formation, bone mass, and bone strength in a rat model of postmenopausal osteoporosis. J Bone Miner Res. 2009; 24: 578-588.
7. Li X, Warmington KS, Niu QT, et al. Inhibition of sclerostin by monoclonal antibody increases bone formation, bone mass, and bone strength in aged male rats. J Bone Miner Res. 2010; 25: 2647-2656.
8. Padhi D, Jang G, Stouch B, Fang L, Posvar E,. Single-dose, placebo-controlled, randomized study of AMG 785, a sclerostin monoclonal antibody. J Bone Miner Res. 2011; 26: 19-26.
9. Power J, Poole KE, van Bezooijen R, et al. Sclerostin and the regulation of bone formation: Effects in hip osteoarthritis and femoral neck fracture. J Bone Miner Res. 2010; 25: 1867-1876.
10. Kusu N, Laurikkala J, Imanishi M, et al. Sclerostin is a novel secreted osteoclast-derived bone morphogenetic protein antagonist with unique ligand specificity. J Biol Chem. 2003; 278: 24113-24117. (Pubitemid 36830246)
11. Winkler DG, Sutherland MK, Geoghegan JC, et al. Osteocyte control of bone formation via sclerostin, a novel BMP antagonist. Embo J. 2003; 22: 6267-6276. (Pubitemid 37522584)
12. Sutherland MK, Geoghegan JC, Yu C, Winkler DG, Latham JA,. Unique regulation of SOST, the sclerosteosis gene, by BMPs and steroid hormones in human osteoblasts. Bone. 2004; 35: 448-454. (Pubitemid 38953192)
13. van Bezooijen RL, Roelen BA, Visser A, et al. Sclerostin is an osteocyte-expressed negative regulator of bone formation, but not a classical BMP antagonist. J Exp Med. 2004; 199: 805-814. (Pubitemid 38375200)
14. Winkler DG, Sutherland MS, Ojala E, et al. Sclerostin inhibition of Wnt-3a-induced C3H10T1/2 cell differentiation is indirect and mediated by bone morphogenetic proteins. J Biol Chem. 2005; 280: 2498-2502. (Pubitemid 40189350)
15. Li X, Zhang Y, Kang H, et al. Sclerostin binds to LRP5/6 and antagonizes canonical Wnt signaling. J Biol Chem. 2005; 280: 19883-19887. (Pubitemid 41379516)
16. van Bezooijen RL, Svensson JP, Eefting D, et al. Wnt but not BMP signaling is involved in the inhibitory action of sclerostin on BMP-stimulated bone formation. J Bone Miner Res. 2007; 22: 19-28. (Pubitemid 46032593)
17. Oliver LLHC, Morvan F, Hu S, Lu C, Bauer M, Kneissel M,. LRP4 is a novel osteoblast and osteocyte expressed specific facilitator of SOST-mediated inhibition of in vitro bone formation. J Bone Miner Res. 2009; 24 (Suppl 1): Available at 9e29961e29977a29972.
18. Choi HY, Dieckmann M, Herz J, Niemeier A,. Lrp4, a novel receptor for Dickkopf 1 and sclerostin, is expressed by osteoblasts and regulates bone growth and turnover in vivo. PLoS One. 2009; 4: e7930.
19. Krishnan V, Bryant HU, Macdougald OA,. Regulation of bone mass by Wnt signaling. J Clin Invest. 2006; 116: 1202-1209.
20. Silvestrini G, Ballanti P, Leopizzi M, et al. Effects of intermittent parathyroid hormone (PTH) administration on SOST mRNA and protein in rat bone. J Mol Histol. 2007; 38: 261-269. (Pubitemid 47106897)
21. Shoback D,. Update in osteoporosis and metabolic bone disorders. J Clin Endocrinol Metab. 2007; 92: 747-753. (Pubitemid 46465635)
22. Bellido T, Ali AA, Gubrij I, et al. Chronic elevation of parathyroid hormone in mice reduces expression of sclerostin by osteocytes: a novel mechanism for hormonal control of osteoblastogenesis. Endocrinology. 2005; 146: 4577-4583. (Pubitemid 41446595)
23. Atkins GJ, Welldon KJ, Halbout P, Findlay DM,. Strontium ranelate treatment of human primary osteoblasts promotes an osteocyte-like phenotype while eliciting an osteoprotegerin response. Osteoporos Int. 2009; 20: 653-664.
24. Ohyama Y, Nifuji A, Maeda Y, Amagasa T, Noda M,. Spaciotemporal association and bone morphogenetic protein regulation of sclerostin and osterix expression during embryonic osteogenesis. Endocrinology. 2004; 145: 4685-4692. (Pubitemid 39281462)
25. Poole KE, van Bezooijen RL, Loveridge N, et al. Sclerostin is a delayed secreted product of osteocytes that inhibits bone formation. Faseb J. 2005; 19: 1842-1844. (Pubitemid 41598769)
26. Irie K, Ejiri S, Sakakura Y, Shibui T, Yajima T,. Matrix mineralization as a trigger for osteocyte maturation. J Histochem Cytochem. 2008; 56: 561-567. (Pubitemid 351702300)
27. Robling AG, Niziolek PJ, Baldridge LA, et al. Mechanical stimulation of bone in vivo reduces osteocyte expression of sost/sclerostin. J Biol Chem. 2008; 283: 5866-5875.
28. Vincent C, Findlay DM, Welldon KJ, et al. Pro-inflammatory cytokines TNF-related weak inducer of apoptosis (TWEAK) and TNFalpha induce the mitogen-activated protein kinase (MAPK)-dependent expression of sclerostin in human osteoblasts. J Bone Miner Res. 2009; 24: 1434-1449.
29. Barragan-Adjemian C, Nicolella D, Dusevich V, Dallas MR, Eick JD, Bonewald LF,. Mechanism by which MLO-A5 late osteoblasts/early osteocytes mineralize in culture: similarities with mineralization of lamellar bone. Calcif Tissue Int. 2006; 79: 340-353. (Pubitemid 44900157)
30. Martin A, David V, Laurence JS, et al. Degradation of MEPE, DMP1, and release of SIBLING ASARM-peptides (minhibins): ASARM-peptide(s) are directly responsible for defective mineralization in HYP. Endocrinology. 2008; 149: 1757-1772. (Pubitemid 351468353)
31. Addison WN, Masica DL, Gray JJ, McKee MD,. Phosphorylation-dependent inhibition of mineralization by osteopontin ASARM peptides is regulated by PHEX cleavage. J Bone Miner Res. 2010; 25: 695-705.
32. Rowe PS,. The wrickkened pathways of FGF23, MEPE and PHEX. Crit Rev Oral Biol Med. 2004; 15: 264-281. (Pubitemid 44560775)
33. Rowe PS, Kumagai Y, Gutierrez G, et al. MEPE has the properties of an osteoblastic phosphatonin and minhibin. Bone. 2004; 34: 303-319. (Pubitemid 38177612)
34. Yuan B, Takaiwa M, Clemens TL, et al. Aberrant Phex function in osteoblasts and osteocytes alone underlies murine X-linked hypophosphatemia. J Clin Invest. 2008; 118: 722-734. (Pubitemid 351206560)
35. Guo R, Rowe PS, Liu S, Simpson LG, Xiao ZS, Quarles LD,. Inhibition of MEPE cleavage by Phex. Biochem Biophys Res Commun. 2002; 297: 38-45.
36. Rowe PS, Garrett IR, Schwarz PM, et al. Surface plasmon resonance (SPR) confirms that MEPE binds to PHEX via the MEPE-ASARM motif: a model for impaired mineralization in X-linked rickets (HYP). Bone. 2005; 36: 33-46. (Pubitemid 40128272)
37. Addison WN, Nakano Y, Loisel T, Crine P, McKee MD,. MEPE-ASARM peptides control extracellular matrix mineralization by binding to hydroxyapatite: an inhibition regulated by PHEX cleavage of ASARM. J Bone Miner Res. 2008; 23: 1638-1649.
38. Robey PG, Termine JD,. Human bone cells in vitro. Calcif Tissue Int. 1985; 37: 453-460. (Pubitemid 15250110)
39. Fedarko NS, Termine JD, Young MF, Robey PG,. Temporal regulation of hyaluronan and proteoglycan metabolism by human bone cells in vitro. J Biol Chem. 1990; 265: 12200-12209.
40. Findlay DM, Welldon K, Atkins GJ, Howie DW, Zannettino AC, Bobyn D,. The proliferation and phenotypic expression of human osteoblasts on tantalum metal. Biomaterials. 2004; 25: 2215-2227. (Pubitemid 38102377)
41. Gronthos S, Zannettino AC, Graves SE, Ohta S, Hay SJ, Simmons PJ,. Differential cell surface expression of the STRO-1 and alkaline phosphatase antigens on discrete developmental stages in primary cultures of human bone cells. J Bone Miner Res. 1999; 14: 47-56. (Pubitemid 29021603)
42. Stewart K, Walsh S, Screen J, et al. Further characterization of cells expressing STRO-1 in cultures of adult human bone marrow stromal cells. J Bone Miner Res. 1999; 14: 1345-1356. (Pubitemid 29368297)
43. Atkins GJ, Welldon KJ, Holding CA, Haynes DR, Howie DW, Findlay DM,. The induction of a catabolic phenotype in human primary osteoblasts and osteocytes by polyethylene particles. Biomaterials. 2009; 30: 3672-3681.
44. Atkins GJ, Welldon KJ, Wijenayaka AR, Bonewald LF, Findlay DM,. Vitamin K promotes mineralization, osteoblast-to-osteocyte transition, and an anticatabolic phenotype by {gamma}-carboxylation-dependent and -independent mechanisms. Am J Physiol Cell Physiol. 2009; 297: C1358-1367.
45. Atkins GJ, Kostakis P, Pan B, et al. RANKL expression is related to the differentiation state of human osteoblasts. J Bone Miner Res. 2003; 18: 1088-1098. (Pubitemid 37294947)
46. Goding JW, Grobben B, Slegers H,. Physiological and pathophysiological functions of the ecto-nucleotide pyrophosphatase/phosphodiesterase family. Biochim Biophys Acta. 2003; 1638: 1-19. (Pubitemid 36577366)
47. Ho AM, Johnson MD, Kingsley DM,. Role of the mouse ank gene in control of tissue calcification and arthritis. Science. 2000; 289: 265-270. (Pubitemid 30469899)
48. Rowe PS, Matsumoto N, Jo OD, et al. Correction of the mineralization defect in hyp mice treated with protease inhibitors CA074 and pepstatin. Bone. 2006; 39: 773-786. (Pubitemid 44335882)
49. Chan A, van Bezooijen RL, Lowik CW,. A new paradigm in the treatment of osteoporosis: Wnt pathway proteins and their antagonists. Curr Opin Investig Drugs. 2007; 8: 293-298. (Pubitemid 46557989)
50. Rey JP, Ellies DL,. Wnt modulators in the biotech pipeline. Dev Dyn. 239: 102-114.
51. Drake MT, Srinivasan B, Modder UI, et al. Effects of parathyroid hormone treatment on circulating sclerostin levels in postmenopausal women. J Clin Endocrinol Metab. 2010; 95: 5056-5062.
52. Gaudio A, Pennisi P, Bratengeier C, et al. Increased sclerostin serum levels associated with bone formation and resorption markers in patients with immobilization-induced bone loss. J Clin Endocrinol Metab. 2010; 95: 2248-2253.
53. Modder UI, Clowes JA, Hoey K, et al. Regulation of circulating sclerostin levels by sex steroids in women and in men. J Bone Miner Res. 2011; 26: 27-34.
54. Jager A, Gotz W, Lossdorfer S, Rath-Deschner B,. Localization of SOST/sclerostin in cementocytes in vivo and in mineralizing periodontal ligament cells in vitro. J Periodontal Res. 2009; 45: 246-254.
55. van Bezooijen RL, Bronckers AL, Gortzak RA, et al. Sclerostin in mineralized matrices and van Buchem disease. J Dent Res. 2009; 88: 569-574.
56. Wetterwald A, Hoffstetter W, Cecchini MG, et al. Characterization and cloning of the E11 antigen, a marker expressed by rat osteoblasts and osteocytes. Bone. 1996; 18: 125-132. (Pubitemid 26092592)
57. Zhang K, Barragan-Adjemian C, Ye L, et al. E11/gp38 selective expression in osteocytes: regulation by mechanical strain and role in dendrite elongation. Mol Cell Biol. 2006; 26: 4539-4552. (Pubitemid 43877574)
58. Argiro L, Desbarats M, Glorieux FH, Ecarot B,. Mepe, the gene encoding a tumor-secreted protein in oncogenic hypophosphatemic osteomalacia, is expressed in bone. Genomics. 2001; 74: 342-351. (Pubitemid 32675358)
59. Gowen LC, Petersen DN, Mansolf AL, et al. Targeted disruption of the osteoblast/osteocyte factor 45 gene (OF45) results in increased bone formation and bone mass. J Biol Chem. 2003; 278: 1998-2007. (Pubitemid 36801442)
60. Qin C, D'Souza R, Feng JQ,. Dentin matrix protein 1 (DMP1): new and important roles for biomineralization and phosphate homeostasis. J Dent Res. 2007; 86: 1134-1141.
61. Feng JQ, Ward LM, Liu S, et al. Loss of DMP1 causes rickets and osteomalacia and identifies a role for osteocytes in mineral metabolism. Nat Genet. 2006; 38: 1310-1315. (Pubitemid 44646294)
62. Francis F, Hennig S, Korn B, et al. A gene (PEX) with homologies to endopeptidases is mutated in patients with X-linked hypophosphatemic rickets. The HYP Consortium. Nat Genet. 1995; 11: 130-136.
63. Yamazaki Y, Okazaki R, Shibata M, et al. Increased circulatory level of biologically active full-length FGF-23 in patients with hypophosphatemic rickets/osteomalacia. J Clin Endocrinol Metab. 2002; 87: 4957-4960. (Pubitemid 35316332)
64. Xiao ZS, Crenshaw M, Guo R, Nesbitt T, Drezner MK, Quarles LD,. Intrinsic mineralization defect in Hyp mouse osteoblasts. Am J Physiol. 1998; 275: E700-708.
65. Liu S, Zhou J, Tang W, Jiang X, Rowe DW, Quarles LD,. Pathogenic role of Fgf23 in Hyp mice. Am J Physiol Endocrinol Metab. 2006; 291: E38-49. (Pubitemid 44035308)
66. Yuan B, Meudt J, Zhang R, Xing Y, Feng J, Drezner MK,. Increased SOST production: A factor underlying abnormal bone mineralization in X-linked hypophosphatemia. J Bone Miner Res. 2009; 24 (Suppl 1): Available at.
67. Liu S, Tang W, Fang J, et al. Novel regulators of Fgf23 expression and mineralization in Hyp bone. Mol Endocrinol. 2009; 23: 1505-1518.