WNT signaling in osteoarthritis and osteoporosis: What is the biological significance for the clinician?

Current Rheumatology Reports

Volumn 11, Issue 1, 2009, Pages 23-30

  Lodewyckx, Liesbet ^a   Lories, Rik J U ^a  

^a UNIVERSITY OF LEUVEN   (Belgium)

Author keywords

[No Author keywords available]

Indexed keywords

ARGININE; AXIN; AXIN 2; BETA CATENIN; COLLAGEN TYPE 2; CYCLIN D1; DICKKOPF 1 PROTEIN; ESTROGEN RECEPTOR ALPHA; FRIZZLED PROTEIN; LOW DENSITY LIPOPROTEIN RECEPTOR RELATED PROTEIN 5; MYC PROTEIN; OSTEOPROTEGERIN; PROTEIN C JUN; SECRETED FRIZZLED RELATED PROTEIN 1; SECRETED FRIZZLED RELATED PROTEIN 2; SECRETED FRIZZLED RELATED PROTEIN 4; UNCLASSIFIED DRUG; WNT PROTEIN; FRZB PROTEIN; GLYCOPROTEIN;

AMINO ACID SUBSTITUTION; BONE DENSITY; BONE MASS; CARTILAGE CELL; CHROMOSOME 11Q; DOWN REGULATION; FRAMESHIFT MUTATION; GENE EXPRESSION; GENE FUNCTION; GENE IDENTIFICATION; GENE TARGETING; GENETIC ANALYSIS; GENETIC SUSCEPTIBILITY; GENETIC VARIABILITY; HUMAN; MICROARRAY ANALYSIS; NONHUMAN; OSSIFICATION; OSTEOARTHRITIS; OSTEOPOROSIS; PHENOTYPE; QUANTITATIVE TRAIT LOCUS; REVIEW; SIGNAL TRANSDUCTION; SINGLE NUCLEOTIDE POLYMORPHISM; UPREGULATION; ANIMAL; DISEASE MODEL; GENETICS; METABOLISM;

ANIMALS; DISEASE MODELS, ANIMAL; GLYCOPROTEINS; HUMANS; OSTEOARTHRITIS; OSTEOPOROSIS; SIGNAL TRANSDUCTION; WNT PROTEINS;

EID: 63449094524     PISSN: 15233774     EISSN: 15346307     Source Type: Journal    
DOI: 10.1007/s11926-009-0004-6     Document Type: Review

References (50)

1. Gordon MDM Nusse R: Wnt signaling: multiple pathways, multiple receptors, and multiple transcription factors. J Biol Chem 2006, 281:22429-22433.
2. Tu X, Joeng KS, Nakayama KI, et al.: Noncanonical Wnt signaling through G protein-linked PKCdelta activation promotes bone formation. Dev Cell 2007, 12:113-127.
3. Gong Y, Slee RB, Fukai N, et al.: LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development. Cell 2001, 107:513-523.
4. MacDonald BT, Joiner DM, Oyserman SM, et al.: Bone mass is inversely proportional to Dkk1 levels in mice. Bone 2007, 41:331-339.
5. Balemans W, Van Hul W: The genetics of low-density lipoprotein receptor-related protein 5 in bone: A story of extremes. Endocrinology 2007, 148:2622-2629.
6. Richards JB, Rivadeneira F, Inouye M, et al.: Bone mineral density, osteoporosis, and osteoporotic fractures: A genomewide association study. Lancet 2008, 371:1505-1512.
7. van Meurs JB, Trikalinos TA, Ralston SH, et al.: Largescale analysis of association between LRP5 and LRP6 variants and osteoporosis. JAMA 2008, 299:1277-1290.
8. Grundberg E, Lau EM, Lorentzson M, et al.: Large-scale association study between two coding LRP5 gene polymorphisms and bone phenotypes and fractures in men. Osteoporos Int 2007, 19:829-837.
9. van Meurs JB, Rivadeneira F, Jhamai M, et al.: Common genetic variation of the low-density lipoprotein receptor-related protein 5 and 6 genes determines fracture risk in elderly white men. J Bone Miner Res 2006, 21:141-150.
10. Kaufman JM, Ostertag A, Saint-Pierre A, et al.: Genomewide linkage screen of bone mineral density (BMD) in European pedigrees ascertained through a male relative with low BMD values: Evidence for Quantitative Trait Loci on 17q21-23, 11q12-13, 13q12-14 and 22q11. J Clin Endocrinol Metab 2008 (in press).
11. Kiel DP, Demissie S, Dupuis J, et al.: Genome-wide association with bone mass and geometry in the Framingham Heart Study. BMC Med Genet 2007, 8(Suppl 1):S14.
12. Kato M, Patel MS, Levasseur R, et al.: Cbfa1-independent decrease in osteoblast proliferation, osteopenia, and persistent embryonic eye vascularization in mice deficient in Lrp5, a Wnt coreceptor. J Cell Biol 2002, 157:303-314.
13. Akhter MP, Wells DJ, Short SJ, et al.: Bone biomechanical properties in LRP5 mutant mice. Bone 2004, 35:162-169.
14. Babij P, Zhao W, Small C, et al.: High bone mass in mice expressing a mutant LRP5 gene. J Bone Miner Res 2003, 18:960-974.
15. Holmen SL, Giambernardi TA, Zylstra CR, et al.: Decreased BMD and limb deformities in mice carrying mutations in both Lrp5 and Lrp6. J Bone Miner Res 2004, 19:2033-2040.
16. Bodine PV, Zhao W, Kharode YP, et al.: The Wnt antagonist secreted frizzled-related protein-1 is a negative regulator of trabecular bone formation in adult mice. Mol Endocrinol 2004, 18:1222-1237.
17. Lories RJ, Peeters J, Bakker A, et al.: Articular cartilage and biomechanical properties of the long bones in Frzbknockout mice. Arthritis Rheum 2007, 56:4095-4103.
18. Bodine PV, Billiard J, Moran RA, et al.: The Wnt antagonist secreted frizzled-related protein-1 controls osteoblast and osteocyte apoptosis. J Cell Biochem 2005, 96:1212-1230.
19. Hausler KD, Horwood NJ, Chuman Y, et al.: Secreted frizzled-related protein-1 inhibits RANKL-dependent osteoclast formation. J Bone Miner Res 2004, 19:1873-1881.
20. Nakanishi R, Shimizu M, Mori M, et al.: Secreted frizzled-related protein 4 is a negative regulator of peak BMD in SAMP6 mice. J Bone Miner Res 2006, 21:1713-1721.
21. Nakanishi R, Akiyama H, Kimura H, et al.: Osteoblast-targeted expression of Sfrp4 in mice results in low bone mass. J Bone Miner Res 2008, 23:271-277.
22. Mukhopadhyay M, Shtrom S, Rodriguez-Esteban C, et al.: Dickkopf1 is required for embryonic head induction and limb morphogenesis in the mouse. Dev Cell 2001, 1:423-434.
23. Li X, Liu P, Liu W, et al.: Dkk2 has a role in terminal osteoblast differentiation and mineralized matrix formation. Nat Genet 2005, 37:945-952.
24. Morvan F, Boulukos K, Clement-Lacroix P, et al.: Deletion of a single allele of the Dkk1 gene leads to an increase in bone formation and bone mass. J Bone Miner Res 2006, 21:934-945.
25. Sawakami K, Robling AG, Ai M, et al.: The Wnt co-receptor LRP5 is essential for skeletal mechanotransduction but not for the anabolic bone response to parathyroid hormone treatment. J Biol Chem 2006, 281:23698-23711.
26. Lau HH, Ng MY, Cheung WM, et al.: Assessment of linkage and association of 13 genetic loci with bone mineral density. J Bone Miner Metab 2006, 24:226-234.
27. Robinson JA, Chatterjee-Kishore M, Yaworsky PJ, et al.: Wnt/beta-catenin signaling is a normal physiological response to mechanical loading in bone. J Biol Chem 2006, 281:31720-31728.
28. Damien E, Price JS, Lanyon LE: Mechanical strain stimulates osteoblast proliferation through the estrogen receptor in males as well as females. J Bone Miner Res 2000, 15:2169-2177.
29. Zaman G, Jessop HL, Muzylak M, et al.: Osteocytes use estrogen receptor alpha to respond to strain but their ERalpha content is regulated by estrogen. J Bone Miner Res 2006, 21:1297-1306.
30. Armstrong VJ, Muzylak M, Sunters A, et al.: Wnt/beta-catenin signaling is a component of osteoblastic bone cell early responses to load-bearing and requires estrogen receptor alpha. J Biol Chem 2007, 282:20715-20727.
31. Foo C, Frey S, Yang HH, et al.: Downregulation of beta-catenin and transdifferentiation of human osteoblasts to adipocytes under estrogen deficiency. Gynecol Endocrinol 2007, 23:535-540.
32. Ohnaka K, Taniguchi H, Kawate H, et al.: Glucocorticoid enhances the expression of dickkopf-1 in human osteoblasts: Novel mechanism of glucocorticoid-induced osteoporosis. Biochem Biophys Res Commun 2004, 318:259-264.
33. Smith E, Frenkel B: Glucocorticoids inhibit the transcriptional activity of LEF/TCF in differentiating osteoblasts in a glycogen synthase kinase-3beta-dependent and -independent manner. J Biol Chem 2005, 280:2388-2394.
34. Hurson CJ, Butler JS, Keating DT, et al.: Gene expression analysis in human osteoblasts exposed to dexamethasone identifies altered developmental pathways as putative drivers of osteoporosis. BMC Musculoskelet Disord 2007, 8:12.
35. Yao W, Cheng Z, Busse C, et al.: Glucocorticoid excess in mice results in early activation of osteoclastogenesis and adipogenesis and prolonged suppression of osteogenesis: A longitudinal study of gene expression in bone tissue from glucocorticoid-treated mice. Arthritis Rheum 2008, 58:1674-1686.
36. Valdes AM, Doherty M, Spector TD: The additive effect of individual genes in predicting risk of knee osteoarthritis. Ann Rheum Dis 2008, 67:124-127.
37. Loughlin J, Dowling B, Chapman K, et al.: Functional variants within the secreted frizzled-related protein 3 gene are associated with hip osteoarthritis in females. Proc Natl Acad Sci U S A 2004, 101:9757-9762.
38. Min JL, Meulenbelt I, Riyazi N, et al.: Association of the Frizzled-related protein gene with symptomatic osteoarthritis at multiple sites. Arthritis Rheum 2005, 52:1077-1080.
39. Lories RJ, Boonen S, Peeters J, et al.: Evidence for a differential association of the Arg200Trp single-nucleotide polymorphism in FRZB with hip osteoarthritis and osteoporosis. Rheumatology (Oxford) 2006, 45:113-114.
40. Lane NE, Lian K, Nevitt MC, et al.: Frizzled-related protein variants are risk factors for hip osteoarthritis. Arthritis Rheum 2006, 54:1246-1254.
41. Valdes AM, Loughlin J, Oene MV, et al.: Sex and ethnic differences in the association of ASPN, CALM1, COL2A1, COMP, and FRZB with genetic susceptibility to osteoarthritis of the knee. Arthritis Rheum 2007, 56:137-146.
42. Kerkhof JM, Uitterlinden AG, Valdes AM, et al.: Radiographic osteoarthritis at three joint sites and FRZB, LRP5, and LRP6 polymorphisms in two population-based cohorts. Osteoarthritis Cartilage 2008 (in press).
43. Smith AJ, Gidley J, Sandy JR, et al.: Haplotypes of the low-density lipoprotein receptor-related protein 5 (LRP5) gene: Are they a risk factor in osteoarthritis? Osteoarthritis Cartilage 2005, 13:608-613.
44. Urano T, Shiraki M, Narusawa K, et al.: Q89R polymorphism in the LDL receptor-related protein 5 gene is associated with spinal osteoarthritis in postmenopausal Japanese women. Spine 2007, 32:25-29.
45. Dell'Accio F, De Bari C, El Tawil NM, et al.: Activation of WNT and BMP signaling in adult human articular cartilage following mechanical injury. Arthritis Res Ther 2006, 8:R139.
46. Dell'Accio F, De Bari C, Eltawil NM, et al.: Identification of the molecular response of articular cartilage to injury, by microarray screening: Wnt-16 expression and signaling after injury and in osteoarthritis. Arthritis Rheum 2008, 58:1410-1421.
47. Appleton CT, Pitelka V, Henry J, Beier F: Global analyses of gene expression in early experimental osteoarthritis. Arthritis Rheum 2007, 56:1854-1868.
48. Zhu M, Chen M, Zuscik M, et al.: Inhibition of betacatenin signaling in articular chondrocytes results in articular cartilage destruction. Arthritis Rheum 2008, 58:2053-2064.
49. Dequeker J, Aerssens J, Luyten FP: Osteoarthritis and osteoporosis: clinical and research evidence of inverse relationship. Aging Clin Exp Res 2003, 15:426-439.
50. Lane NE, Nevitt MC, Lui LY, et al.: Wnt signaling antagonists are potential prognostic biomarkers for the progression of radiographic hip osteoarthritis in elderly Caucasian women. Arthritis Rheum 2007, 56:3319-3325.