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Article Open Access

Sclerostin expression in the subchondral bone of patients with knee osteoarthritis

  • Authors:
    • Long Wu
    • Haohui Guo
    • Kening Sun
    • Xin Zhao
    • Tao Ma
    • Qunhua Jin
  • View Affiliations / Copyright

    Affiliations: Department of Orthopedics, The General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China
    Copyright: © Wu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1395-1402
    |
    Published online on: September 19, 2016
       https://doi.org/10.3892/ijmm.2016.2741
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Abstract

The aim of this study was to assess the expression of β-catenin, transcription factor-4 (TCF-4) and sclerostin in the subchondral bone of patients with primary knee osteoarthritis (OA). Tibial plateau specimens from patients with OA who underwent total knee arthroplasty were classified into the early stage (n=15), intermediate stage (n=13) and late stage (n=17) groups using the Mankin score. Structural parameters, including total articular cartilage (TAC), subchondral bone plate (SCP) thickness and trabecular bone volume (BV/TV), were assessed using Image-Pro Plus 6.0 analysis software. Subsequently, β-catenin and sclerostin expression levels in subchondral bone were determined by immunohistochemistry. In addition, the mRNA and protein levels of β-catenin, TCF-4 and sclerostin were evaluated by RT-qPCR and western blot analysis, respectively. As regards the cartilage and subchondral bone structural parameters, TAC was reduced, while SCP thickness and BV/TV were increased due to OA, with significant differences observed among the different stages (all P<0.05). The results of immunohistochemistry revealed that the β-catenin levels in the intermediate- and late-stage samples were significantly increased, while the levels of sclerostin were markedly decreased compared with the values in the early-stage samples (all P<0.05). Compared with the intermediate-stage samples, the sclerostin levels were decreased, and SCP thickness and the β-catenin levels were increased in the late-stage samples (all P<0.05). The results of RT-qPCR and western blot analysis revealed that the β-catenin and TCF-4 mRNA and protein levels in the intermediate- and late-stage samples were significantly increased, while sclerostin expression was significantly decreased compared with the early-stage samples; a similar trend was observed between the intermediate- and late-stage samples (all P<0.05). Finally, the β-catenin and TCF-4 levels positively correlated with the Mankin scores, while there was a negative correlation with sclerostin expression. Our findings demonstrate that sclerostin expression is closely associated with the degree of joint damage in patients with OA, confirming its involvement in the development of OA.
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View References

1 

Felson DT: Developments in the clinical understanding of osteoarthritis. Arthritis Res Ther. 11:2032009. View Article : Google Scholar : PubMed/NCBI

2 

Felson DT and Neogi T: Osteoarthritis: is it a disease of cartilage or of bone? Arthritis Rheum. 50:341–344. 2004. View Article : Google Scholar : PubMed/NCBI

3 

Song L, Liu M, Ono N, Bringhurst FR, Kronenberg HM and Guo J: Loss of wnt/β-catenin signaling causes cell fate shift of preosteoblasts from osteoblasts to adipocytes. J Bone Miner Res. 27:2344–2358. 2012. View Article : Google Scholar : PubMed/NCBI

4 

Chen B, Li XD, Liu DX, Wang H, Xie P, Liu ZY, Hou GQ, Chang B and Du SX: Canonical Wnt signaling is required for Panax notoginseng saponin-mediated attenuation of the RANKL/OPG ratio in bone marrow stromal cells during osteogenic differentiation. Phytomedicine. 19:1029–1034. 2012. View Article : Google Scholar : PubMed/NCBI

5 

Spencer GJ, Utting JC, Etheridge SL, Arnett TR and Genever PG: Wnt signalling in osteoblasts regulates expression of the receptor activator of NFkappaB ligand and inhibits osteoclastogenesis in vitro. J Cell Sci. 119:1283–1296. 2006. View Article : Google Scholar : PubMed/NCBI

6 

Moester MJ, Papapoulos SE, Löwik CW and van Bezooijen RL: Sclerostin: current knowledge and future perspectives. Calcif Tissue Int. 87:99–107. 2010. View Article : Google Scholar : PubMed/NCBI

7 

van Bezooijen RL, Roelen BA, Visser A, van der Wee-Pals L, de Wilt E, Karperien M, Hamersma H, Papapoulos SE, ten Dijke P and Löwik CW: Sclerostin is an osteocyte-expressed negative regulator of bone formation, but not a classical BMP antagonist. J Exp Med. 199:805–814. 2004. View Article : Google Scholar : PubMed/NCBI

8 

Poole KE, van Bezooijen RL, Loveridge N, Hamersma H, Papapoulos SE, Löwik CW and Reeve J: Sclerostin is a delayed secreted product of osteocytes that inhibits bone formation. FASEB J. 19:1842–1844. 2005.PubMed/NCBI

9 

Li X, Zhang Y, Kang H, Liu W, Liu P, Zhang J, Harris SE and Wu D: Sclerostin binds to LRP5/6 and antagonizes canonical Wnt signaling. J Biol Chem. 280:19883–19887. 2005. View Article : Google Scholar : PubMed/NCBI

10 

Semënov M, Tamai K and He X: SOST is a ligand for LRP5/LRP6 and a Wnt signaling inhibitor. J Biol Chem. 280:26770–26775. 2005. View Article : Google Scholar : PubMed/NCBI

11 

Altman RD: Criteria for classification of clinical osteoarthritis. J Rheumatol Suppl. 27:10–12. 1991.PubMed/NCBI

12 

Zhang W, Moskowitz RW, Nuki G, Abramson S, Altman RD, Arden N, Bierma-Zeinstra S, Brandt KD, Croft P, Doherty M, et al: OARSI recommendations for the management of hip and knee osteoarthritis, Part II: OARSI evidence-based, expert consensus guidelines. Osteoarthritis Cartilage. 16:137–162. 2008. View Article : Google Scholar : PubMed/NCBI

13 

Bobinac D, Spanjol J, Zoricic S and Maric I: Changes in articular cartilage and subchondral bone histomorphometry in osteoarthritic knee joints in humans. Bone. 32:284–290. 2003. View Article : Google Scholar : PubMed/NCBI

14 

Burr DB: Anatomy and physiology of the mineralized tissues: role in the pathogenesis of osteoarthro sis. Osteoarthritis Cartilage. 12(Suppl A): S20–30. 2004. View Article : Google Scholar

15 

Prasadam I, van Gennip S, Friis T, Shi W, Crawford R and Xiao Y: ERK-1/2 and p38 in the regulation of hypertrophic changes of normal articular cartilage chondrocytes induced by osteoarthritic subchondral osteoblasts. Arthritis Rheum. 62:1349–1360. 2010. View Article : Google Scholar : PubMed/NCBI

16 

Sanchez C, Deberg MA, Piccardi N, Msika P, Reginster JY and Henrotin YE: Osteoblasts from the sclerotic subchondral bone downregulate aggrecan but upregulate metalloproteinases expression by chondrocytes. This effect is mimicked by interleukin-6, -1beta and oncostatin M pre-treated non-sclerotic osteoblasts. Osteoarthritis Cartilage. 13:979–987. 2005. View Article : Google Scholar : PubMed/NCBI

17 

Karsdal MA, Leeming DJ, Dam EB, Henriksen K, Alexandersen P, Pastoureau P, Altman RD and Christiansen C: Should subchondral bone turnover be targeted when treating osteoarthritis? Osteoarthritis Cartilage. 16:638–646. 2008. View Article : Google Scholar : PubMed/NCBI

18 

Trouvin AP and Goëb V: Receptor activator of nuclear factor-κB ligand and osteoprotegerin: maintaining the balance to prevent bone loss. Clin Interv Aging. 5:345–354. 2010.

19 

Bodine PV: Wnt signaling control of bone cell apoptosis. Cell Res. 18:248–253. 2008. View Article : Google Scholar : PubMed/NCBI

20 

Ma B, Zhong L, van Blitterswijk CA, Post JN and Karperien M: T cell factor 4 is a pro-catabolic and apoptotic factor in human articular chondrocytes by potentiating nuclear factor κB signaling. J Biol Chem. 288:17552–17558. 2013. View Article : Google Scholar : PubMed/NCBI

21 

Winkler DG, Sutherland MK, Geoghegan JC, Yu C, Hayes T, Skonier JE, Shpektor D, Jonas M, Kovacevich BR, Staehling-Hampton K, et al: Osteocyte control of bone formation via sclerostin, a novel BMP antagonist. EMBO J. 22:6267–6276. 2003. View Article : Google Scholar : PubMed/NCBI

22 

van Bezooijen RL, Bronckers AL, Gortzak RA, Hogendoorn PC, van der Wee-Pals L, Balemans W, Oostenbroek HJ, Van Hul W, Hamersma H, Dikkers FG, et al: Sclerostin in mineralized matrices and van Buchem disease. J Dent Res. 88:569–574. 2009. View Article : Google Scholar : PubMed/NCBI

23 

Krause C, Korchynskyi O, de Rooij K, Weidauer SE, de Gorter DJ, van Bezooijen RL, Hatsell S, Economides AN, Mueller TD, Löwik CW and ten Dijke P: Distinct modes of inhibition by sclerostin on bone morphogenetic protein and Wnt signaling pathways. J Biol Chem. 285:41614–41626. 2010. View Article : Google Scholar : PubMed/NCBI

24 

Robling AG, Niziolek PJ, Baldridge LA, Condon KW, Allen MR, Alam I, Mantila SM, Gluhak-Heinrich J, Bellido TM, Harris SE, et al: Mechanical stimulation of bone in vivo reduces osteocyte expression of Sost/sclerostin. J Biol Chem. 283:5866–5875. 2008. View Article : Google Scholar

25 

Lin C, Jiang X, Dai Z, Guo X, Weng T, Wang J, Li Y, Feng G, Gao X and He L: Sclerostin mediates bone response to mechanical unloading through antagonizing Wnt/beta-catenin signaling. J Bone Miner Res. 24:1651–1661. 2009. View Article : Google Scholar : PubMed/NCBI

26 

Bonewald LF and Johnson ML: Osteocytes, mechanosensing and Wnt signaling. Bone. 42:606–615. 2008. View Article : Google Scholar : PubMed/NCBI

27 

Burr DB: The importance of subchondral bone in the progression of osteoarthritis. J Rheumatol Suppl. 70:77–80. 2004.PubMed/NCBI

28 

Goldring MB and Goldring SR: Articular cartilage and subchondral bone in the pathogenesis of osteoarthritis. Ann N Y Acad Sci. 1192:230–237. 2010. View Article : Google Scholar : PubMed/NCBI

29 

Madry H, van Dijk CN and Mueller-Gerbl M: The basic science of the subchondral bone. Knee Surg Sports Traumatol Arthrosc. 18:419–433. 2010. View Article : Google Scholar : PubMed/NCBI

30 

Funck-Brentano T, Bouaziz W, Marty C, Geoffroy V, Hay E and Cohen-Solal M: Dkk-1-mediated inhibition of Wnt signaling in bone ameliorates osteoarthritis in mice. Arthritis Rheumatol. 66:3028–3039. 2014. View Article : Google Scholar : PubMed/NCBI

31 

Ominsky M, Warmington K, Asuncion F, Tan H, Grisanti M, Geng Z, Stephens T, Henry A, Lawson A, Lightwood D, et al: Sclerostin monoclonal antibody treatment increases bone strength in aged osteopenic ovariectomized rats. J Bone Miner Res. 21(Suppl 1): S442006.

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Copy and paste a formatted citation
Spandidos Publications style
Wu L, Guo H, Sun K, Zhao X, Ma T and Jin Q: Sclerostin expression in the subchondral bone of patients with knee osteoarthritis. Int J Mol Med 38: 1395-1402, 2016.
APA
Wu, L., Guo, H., Sun, K., Zhao, X., Ma, T., & Jin, Q. (2016). Sclerostin expression in the subchondral bone of patients with knee osteoarthritis. International Journal of Molecular Medicine, 38, 1395-1402. https://doi.org/10.3892/ijmm.2016.2741
MLA
Wu, L., Guo, H., Sun, K., Zhao, X., Ma, T., Jin, Q."Sclerostin expression in the subchondral bone of patients with knee osteoarthritis". International Journal of Molecular Medicine 38.5 (2016): 1395-1402.
Chicago
Wu, L., Guo, H., Sun, K., Zhao, X., Ma, T., Jin, Q."Sclerostin expression in the subchondral bone of patients with knee osteoarthritis". International Journal of Molecular Medicine 38, no. 5 (2016): 1395-1402. https://doi.org/10.3892/ijmm.2016.2741
Copy and paste a formatted citation
x
Spandidos Publications style
Wu L, Guo H, Sun K, Zhao X, Ma T and Jin Q: Sclerostin expression in the subchondral bone of patients with knee osteoarthritis. Int J Mol Med 38: 1395-1402, 2016.
APA
Wu, L., Guo, H., Sun, K., Zhao, X., Ma, T., & Jin, Q. (2016). Sclerostin expression in the subchondral bone of patients with knee osteoarthritis. International Journal of Molecular Medicine, 38, 1395-1402. https://doi.org/10.3892/ijmm.2016.2741
MLA
Wu, L., Guo, H., Sun, K., Zhao, X., Ma, T., Jin, Q."Sclerostin expression in the subchondral bone of patients with knee osteoarthritis". International Journal of Molecular Medicine 38.5 (2016): 1395-1402.
Chicago
Wu, L., Guo, H., Sun, K., Zhao, X., Ma, T., Jin, Q."Sclerostin expression in the subchondral bone of patients with knee osteoarthritis". International Journal of Molecular Medicine 38, no. 5 (2016): 1395-1402. https://doi.org/10.3892/ijmm.2016.2741
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