Role of sclerostin in bone and cartilage and its potential as a therapeutic target in bone diseases

Therapeutic Advances in Musculoskeletal Disease

Volumn 6, Issue 2, 2014, Pages 48-57

  Lewiecki, E Michael ^a  

^a UNIVERSITY OF NEW MEXICO SCHOOL OF MEDICINE   (United States)

Author keywords

anabolic; blosozumab; BPS804; osteoporosis; romosozumab; sclerostin

Indexed keywords

ALENDRONIC ACID; BETA CATENIN; BLOSOZUMAB; BPS 804; LOW DENSITY LIPOPROTEIN RECEPTOR RELATED PROTEIN 5; LOW DENSITY LIPOPROTEIN RECEPTOR RELATED PROTEIN 6; MONOCLONAL ANTIBODY; PARATHYROID HORMONE[1-34]; ROMOSOZUMAB; SCLEROSTIN; UNCLASSIFIED DRUG;

BONE DENSITY; BONE DISEASE; BONE MINERAL; CARTILAGE; CARTILAGE CELL; CELL DIFFERENTIATION; CELL PROLIFERATION; DUAL ENERGY X RAY ABSORPTIOMETRY; GENE EXPRESSION; GENE MUTATION; HUMAN; LUMBAR SPINE; MORPHOMETRICS; NONHUMAN; OSSIFICATION; OSTEOARTHRITIS; OSTEOBLAST; OSTEOLYSIS; OSTEOSCLEROSIS; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; QUALITY OF LIFE; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; UPREGULATION; WNT SIGNALING PATHWAY;

EID: 84896284222     PISSN: 1759720X     EISSN: 17597218     Source Type: Journal    
DOI: 10.1177/1759720X13510479     Document Type: Review

References (52)

1. Adami S. Libanati C. Adachi J. Boonen S. Cummings S. de Gregorio L. et al. (2012) Denosumab administration is not associated with fracture healing complications in postmenopausal women with osteoporosis: results from the FREEDOM trial. J Bone Miner Res 25(Suppl. 1): S478.
2. Agholme F. Li X. Isaksson H. Ke H.Z. Aspenberg P. (2010) Sclerostin antibody treatment enhances metaphyseal bone healing in rats. J Bone Miner Res 25 (11): 2412–2418.
3. Babcook J. Leslie K. Olsen O. Salmon R. Schrader J. (1996) A novel strategy for generating monoclonal antibodies from single, isolated lymphocytes producing antibodies of defined specificities. Proc Natl Acad Sci U S A 93 (15): 7843–7848.
4. Balemans W. Ebeling M. Patel N. van H. Olson P. Dioszegi M. et al. (2001) Increased bone density in sclerosteosis is due to the deficiency of a novel secreted protein (SOST). Hum Mol Genet 10: 537–543.
5. Baron R. Rawadi G. (2007) Targeting the Wnt/beta-catenin pathway to regulate bone formation in the adult skeleton. Endocrinology 148: 2635–2643.
6. Beighton P. Davidson J. Durr L. Hamersma H. (1977) Sclerosteosis – an autosomal recessive disorder. Clin Genet 11: 1–7.
7. Benson C. Robins D. Recker R. Alam J. Chiang A. Mitlak B. et al. (2013) Effect of blosozumab on bone mineral density: results of a phase 2 study of postmenopausal women with low bone mineral density. Bone Abstracts 1: OC5.3.
8. Brunkow M. Gardner J. van N. Paeper B. Kovacevich B. Proll S. et al. (2001) Bone dysplasia sclerosteosis results from loss of the SOST gene product, a novel cystine knot-containing protein. Am J Hum Genet 68: 577–589.
9. Centers for Disease Control and Prevention (2011) Osteoarthritis. Available at: http://www.cdc.gov/arthritis/basics/osteoarthritis.htm (accessed 15 October 2013).
10. Chan B. Fuller E. Russell A. Smith S. Smith M. Jackson M. et al. (2011) Increased chondrocyte sclerostin may protect against cartilage degradation in osteoarthritis. Osteoarthritis Cartilage 19: 874–885.
11. Cipriani C. Irani D. Bilezikian J. (2012) Safety of osteoanabolic therapy: a decade of experience. J Bone Miner Res 27: 2419–2428.
12. Clevers H. (2006) Wnt/beta-catenin signaling in development and disease. Cell 127: 469–480.
13. Cornell C. (2003) Internal fracture fixation in patients with osteoporosis. J Am Acad Orthop Surg 11: 109–119.
14. Cummings S. San Martin J. McClung M. Siris E. Eastell R. Reid I. et al. (2009) Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med 361: 756–765.
15. Delmas P. van de Langerijt L. Watts N. Eastell R. Genant H. Grauer A. et al. (2005) Underdiagnosis of vertebral fractures is a worldwide problem: the IMPACT study. J Bone Miner Res 20: 557–563.
16. Foley K. Foster S. Meadows E. Baser O. Long S. (2007) Assessment of the clinical management of fragility fractures and implications for the new HEDIS osteoporosis measure. Med Care 45: 902–906.
17. Gardner J. van Bezooijen R. Mervis B. Hamdy N. Lowik C. Hamersma H. et al. (2005) Bone mineral density in sclerosteosis; affected individuals and gene carriers. J Clin Endocrinol Metab 90: 6392–6395.
18. Goldhahn J. Feron J. Kanis J. Papapoulos S. Reginster J. Rizzoli R. et al. (2012) Implications for fracture healing of current and new osteoporosis treatments: an ESCEO consensus paper. Calcif Tissue Int 90: 343–353.
19. Goldring M. (2012) Chondrogenesis, chondrocyte differentiation, and articular cartilage metabolism in health and osteoarthritis. Ther Adv Musculoskelet Dis 4: 269–285.
20. Hamersma H. Gardner J. Beighton P. (2003) The natural history of sclerosteosis. Clin Genet 63: 192–197.
21. Kanis J. (2007) Assessment of Osteoporosis at the Primary Health-care Level. Technical report. World Health Organization Collaborating Centre for Metabolic Bone Diseases. Sheffield: University of Sheffield.
22. Kansara M. Tsang M. Kodjabachian L. Sims N. Trivett M. Ehrich M. et al. (2009) Wnt inhibitory factor 1 is epigenetically silenced in human osteosarcoma, and targeted disruption accelerates osteosarcomagenesis in mice. J Clin Invest 119: 837–851.
23. Ke H. Richards W. Li X. Ominsky M. (2012) Sclerostin and Dickkopf-1 as therapeutic targets in bone diseases. Endocr Rev 33: 747–783.
24. Kim J. Liu X. Wang J. Chen X. Zhang H. Kim S. et al. (2013) Wnt signaling in bone formation and its therapeutic potential for bone diseases. Ther Adv Musculoskelet Dis 5: 13–31.
25. Klibanski A. Adams-Campbell L. Bassford T. Blair S. Boden S. Dickersin K. et al. (2001) Osteoporosis prevention, diagnosis, and therapy. JAMA 285: 785–795.
26. Kramer I. Loots G. Studer A. Keller H. Kneissel M. (2010) Parathyroid hormone (PTH)-induced bone gain is blunted in SOST overexpressing and deficient mice. J Bone Miner Res 25: 178–189.
27. Lewiecki E. (2011) New targets for intervention in the treatment of postmenopausal osteoporosis. Nat Rev Rheumatol 7: 631–638.
28. Li X. Ominsky M. Niu Q. Sun N. Daugherty B. D'Agostin D. et al. (2008) Targeted deletion of the sclerostin gene in mice results in increased bone formation and bone strength. J Bone Miner Res 23: 860–869.
29. Li X. Warmington K.S. Niu Q.T. Asuncion F.J. Barrero M. Grisanti M. et al. (2010) Inhibition of sclerostin by monoclonal antibody increases bone formation, bone mass and bone strength in aged male rats. J Bone Miner Res 25 (12): 2647–2656.
30. Li X. Zhang Y. Kang H. Liu W. Liu P. Zhang J. et al. (2005) Sclerostin binds to LRP5/6 and antagonizes canonical Wnt signaling. J Biol Chem 280: 19883–19887.
31. Lin C. Jiang X. Dai Z. Guo X. Weng T. Wang J. et al. (2009) Sclerostin mediates bone response to mechanical unloading through antagonizing Wnt/beta-catenin signaling. J Bone Miner Res 24: 1651–1661.
32. Lories R. Luyten F. (2011) The bone-cartilage unit in osteoarthritis. Nat Rev Rheumatol 7: 43–49.
33. Luyten F. Tylzanowski P. Lories R. (2009) Wnt signaling and osteoarthritis. Bone 44: 522–527.
34. McClung M. Grauer A. Boonen S. Brown J. Diez-Perez A. Langdahl B. et al. (2012) Inhibition of sclerostin with AMG 785 in postmenopausal women with low bone mineral density: phase 2 trial results. J Bone Miner Res 27(Suppl. 1): S8.
35. McColm J. Womack T. Hu L. Tang C. Chiang A. (2012) Blosozumab, a humanized monoclonal antibody against sclerostin, demonstrated anabolic effects on bone in postmenopausal women.J Bone Miner Res 27(Suppl. 1): S9.
36. Neogi T. Zhang Y. (2013) Epidemiology of osteoarthritis. Rheum Dis Clin North Am 39: 1–19.
37. Nusse R. Varmus H. (1982) Many tumors induced by the mouse mammary tumor virus contain a provirus integrated in the same region of the host genome. Cell 31: 99–109.
38. Ominsky M. Li C. Li X. Tan H. Lee E. Barrero M. et al. (2011) Inhibition of sclerostin by monoclonal antibody enhances bone healing and improves bone density and strength of nonfractured bones. J Bone Miner Res 26: 1012–1021.
39. Ominsky M. Samadfan R. Jolette J. Vlasseros F. Smith S. Kostenuik P. et al. (2009) Sclerostin monoclonal antibody stimulates bone formation and improves the strength and density of the fracture callus and lumbar spine in a primate fibular osteotomy model. J Bone Miner Res 24(Suppl. 1): S89–S90.
40. Ominsky M. Vlasseros F. Jolette J. Smith S. Stouch B. Doellgast G. et al. (2010) Two doses of sclerostin antibody in cynomolgus monkeys increases bone formation, bone mineral density, and bone strength. J Bone Miner Res 25: 948–959.
41. Padhi D. Jang G. Stouch B. Fang L. Posvar E. (2011) Single-dose, placebo-controlled, randomized study of AMG 785, a sclerostin monoclonal antibody. J Bone Miner Res 26: 19–26.
42. Robling A. Niziolek P. Baldridge L. Condon K. Allen M. Alam I. et al. (2008) Mechanical stimulation of bone in vivo reduces osteocyte expression of Sost/sclerostin. J Biol Chem 283: 5866–5875.
43. Roudier M. Li X. Niu Q. Pacheco E. Pretorius J. Graham K. et al. (2013) Sclerostin is expressed in articular cartilage but loss or inhibition does not affect cartilage remodeling during aging or following mechanical injury. Arthritis Rheum 65: 721–731.
44. Staehling-Hampton K. Proll S. Paeper B. Zhao L. Charmley P. Brown A. et al. (2002) 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 110: 144–152.
45. Vahle J. Long G. Sandusky G. Westmore M. Ma Y. Sato M. (2004) Bone neoplasms in F 344 rats given teriparatide [rhPTH(1-34)] are dependent on duration of treatment and dose. Toxicol Pathol 32: 426–438.
46. van Bezooijen R. Roelen B. Visser A. van der Wee-Pals L. de Wilt E. Karperien M. et al. (2004) Sclerostin is an osteocyte-expressed negative regulator of bone formation, but not a classical BMP antagonist. J Exp Med 199: 805–814.
47. van Lierop A. Hamdy N. Hamersma H. van Bezooijen R. Power J. Loveridge N. et al. (2011) Patients with sclerosteosis and disease carriers: human models of the effect of sclerostin on bone turnover. J Bone Miner Res 26: 2804–2811.
48. Veverka V. Henry A. Slocombe P. Ventom A. Mulloy B. Muskett F. et al. (2009) Characterization of the structural features and interactions of sclerostin: molecular insight into a key regulator of Wnt-mediated bone formation. J Biol Chem 284: 10890–10900.
49. Wang W. Wang E. Balthasar J. (2008) Monoclonal antibody pharmacokinetics and pharmacodynamics. Clin Pharmacol Ther 84: 548–558.
50. Wergedal J. Veskovic K. Hellan M. Nyght C. Balemans W. Libanati C. et al. (2003) Patients with van Buchem disease, an osteosclerotic genetic disease, have elevated bone formation markers, higher bone density, and greater derived polar moment of inertia than normal. J Clin Endocrinol Metab 88: 5778–5783.
51. Zhu M. Chen M. Zuscik M. Wu Q. Wang Y. Rosier R. et al. (2008) Inhibition of beta-catenin signaling in articular chondrocytes results in articular cartilage destruction. Arthritis Rheum 58: 2053–2064.
52. Zhu M. Tang D. Wu Q. Hao S. Chen M. Xie C. et al. (2009) Activation of beta-catenin signaling in articular chondrocytes leads to osteoarthritis-like phenotype in adult beta-catenin conditional activation mice. J Bone Miner Res 24: 12–21.