Expression of Sclerostin in medial and lateral subchondral bone of the varus osteoarthritic knee plateau_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

SANG Weilin ¹ , JIANG Yafei ¹ ,  CHENG Biao ² , MA Jinzhong ¹ , ZHU Libo ¹ , LU Haiming ¹ , WANG Cong ¹

1. Department of Orthopedics, Clinical Medical School, Shanghai General Hospital of Nanjing Medical University, Shanghai, 201620, P.R.China;
2. Department of Orthopedics, Clinical Medical School, The Affiliated Shanghai No.10 People’s Hospital, Nanjing Medical University, Shanghai, 200072, P.R.China;

Corresponding author：

CHENG Biao, Email: 13681973702@sina.cn

Keywords：

Osteoarthritis; subchondral bone; bone remodeling; Sclerostin

DOI：

10.7507/1002-1892.201610082

Video：

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Objective To study the expression difference of Sclerostin in the medial and lateral subchondral bone of the varus osteoarthritic knee plateau. Methods The tibial plateau was obtained from 20 patients with varus knee osteoarthritis receiving total knee arthroplasty from March to October 2015. There were 8 males and 12 females with an average age of 67.8 years (range, 61-78 years). The mean course of osteoarthritis was 3.2 years (range, 2-5 years). Before operation, the varus angle was 12.0-25.5° (mean, 17.6°) on the X-ray film. Five cases were rated as grade III and 15 cases as grade IV according to Kellgren-Lawrance classification. Micro-CT scan was performed on the medial and lateral subchondral bone to compare the changes of bone structure; bone volume/total volume (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), structure model index (SMI), and the trabecular separation (Tb.Sp) were measured. Immunohistochemistry and real-time fluorescent quantitative PCR were used to test the expressions of Sclerostin protein and sost gene. Results Micro-CT showed that BV/TV, Tb.N, and Tb.Th significantly increased in the medial subchondral bone when compared with the lateral part (P<0.05), but SMI and Tb.Sp significantly reduced (P<0.05). Real-time fluorescent quantitative PCR detection showed that sost gene expression level in the medial subchondral bone (1.000) was significantly lower than that in the lateral part (4.157±2.790) (t=2.371,P=0.040). The percentage of Sclerostin positive cells in the lateral subchondral bone (52.00%±0.19%) was significantly higher than that in the medial subchondral bone (7.20%±0.04%) (t=5.094,P=0.005). Conclusion Sclerostin plays an important role in the subchondral bone remodeling of the varus osteoarthritic knee. And the low expression of Sclerostin may be an important factor to promote bone remodeling and aggravate knee deformity.

Citation： SANG Weilin, JIANG Yafei, CHENG Biao, MA Jinzhong, ZHU Libo, LU Haiming, WANG Cong. Expression of Sclerostin in medial and lateral subchondral bone of the varus osteoarthritic knee plateau. Chinese Journal of Reparative and Reconstructive Surgery, 2017, 31(3): 295-299. doi: 10.7507/1002-1892.201610082 Copy

1.	Funck-Brentano T, Cohen-Solal M. Subchondral bone and osteoarthritis. Curr Opin Rheumatol, 2015, 27(4): 420-426.
2.	Brandt KD, Radin EL, Dieppe PA,et al. Yet more evidence that osteoarthritis is not a cartilage disease. Ann Rheum Dis, 2006, 65(10): 1261-1264.
3.	Radin EL, Rose RM. Role of subchondral bone in the initiation and progression of cartilage damage. Clin Orthop Relat Res, 1986, (213): 34-40.
4.	Sharma AR, Jagga S, Lee SS,et al. Interplay between cartilage and subchondral bone contributing to pathogenesis of osteoarthritis. Int J Mol Sci, 2013, 14(10): 19805-19830.
5.	Botter SM, van Osch GJ, Clockaerts S,et al. Osteoarthritis induction leads to early and temporal subchondral plate porosity in the tibial plateau of mice: an in vivo microfocal computed tomography study. Arthritis Rheum, 2011, 63(9): 2690-2699.
6.	Jaiprakash A, Prasadam I, Feng JQ,et al. Phenotypic characterization of osteoarthritic osteocytes from the sclerotic zones: a possible pathological role in subchondral bone sclerosis. Int J Biol Sci, 2012, 8(3): 406-417.
7.	Pritzker KP, Gay S, Jimenez SA,et al. Osteoarthritis cartilage histopathology: grading and staging. Osteoarthritis Cartilage, 2006, 14(1): 13-29.
8.	Veverka V, Henry AJ, Slocombe PM,et al. Characterization of the structural features and interactions of sclerostin: molecular insight into a key regulator of Wnt-mediated bone formation. J Biol Chem, 2009, 284(16): 10890-10900.
9.	Wu L, Guo H, Sun K,et al. Sclerostin expression in the subchondral bone of patients with knee osteoarthritis. Int J Mol Med, 2016, 38(5): 1395-1402.
10.	Kellgren JH, Lawrence JS. Radiological assessment of osteo-arthrosis. Ann Rheum Dis, 1957, 16(4): 494-502.
11.	Yu DG, Nie SB, Liu FX,et al. Dynamic alterations in microarchitecture, mineralization and mechanical property of subchondral bone in rat medial meniscal tear model of osteoarthritis. Chin Med J (Engl), 2015, 128(21): 2879-2886.
12.	Nevitt MC, Zhang Y, Javaid MK,et al. High systemic bone mineral density increases the risk of incident knee OA and joint space narrowing, but not radiographic progression of existing knee OA: the MOST study. Ann Rheum Dis, 2010, 69(1): 163-168.
13.	Finnilä MA, Thevenot J, Aho OM,et al. Association between subchondral bone structure and osteoarthritis histopathological grade. J Orthop Res, 2016. [Epub ahead of print].
14.	Compton JT, Lee FY. A review of osteocyte function and the emerging importance of sclerostin. J Bone Joint Surg (Am), 2014, 96(19): 1659-1668.
15.	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(9): 5866-5875.
16.	Spatz JM, Wein MN, Gooi JH,et al. The Wnt inhibitor sclerostin is up-regulated by mechanical unloading in osteocytesin vitro. J Biol Chem, 2015, 290(27): 16744-16758.
17.	Goldring SR. The osteocyte: key player in regulating bone turnover. RMD Open, 2015, 1(Suppl 1): e000049.
18.	Chou CH, Wu CC, Song IW,et al. Genome-wide expression profiles of subchondral bone in osteoarthritis. Arthritis Res Ther, 2013, 15(6): R190.
19.	Becker CB. Sclerostin inhibition for osteoporosis——a new approach. N Engl J Med, 2014, 370(5): 476-477.
20.	MacNabb C, Patton D, Hayes JS. Sclerostin antibody therapy for the treatment of osteoporosis: Clinical prospects and challenges. J Osteoporos, 2016, 2016: 6217286.
21.	Appelman-Dijkstra NM, Papapoulos SE. Sclerostin inhibition in the management of osteoporosis. Calcif Tissue Int, 2016, 98(4): 370-380.
22.	Barr AJ, Campbell TM, Hopkinson D,et al. A systematic review of the relationship between subchondral bone features, pain and structural pathology in peripheral joint osteoarthritis. Arthritis Res Ther, 2015, 17(25): 228.

1. Funck-Brentano T, Cohen-Solal M. Subchondral bone and osteoarthritis. Curr Opin Rheumatol, 2015, 27(4): 420-426.
2. Brandt KD, Radin EL, Dieppe PA,et al. Yet more evidence that osteoarthritis is not a cartilage disease. Ann Rheum Dis, 2006, 65(10): 1261-1264.
3. Radin EL, Rose RM. Role of subchondral bone in the initiation and progression of cartilage damage. Clin Orthop Relat Res, 1986, (213): 34-40.
4. Sharma AR, Jagga S, Lee SS,et al. Interplay between cartilage and subchondral bone contributing to pathogenesis of osteoarthritis. Int J Mol Sci, 2013, 14(10): 19805-19830.
5. Botter SM, van Osch GJ, Clockaerts S,et al. Osteoarthritis induction leads to early and temporal subchondral plate porosity in the tibial plateau of mice: an in vivo microfocal computed tomography study. Arthritis Rheum, 2011, 63(9): 2690-2699.
6. Jaiprakash A, Prasadam I, Feng JQ,et al. Phenotypic characterization of osteoarthritic osteocytes from the sclerotic zones: a possible pathological role in subchondral bone sclerosis. Int J Biol Sci, 2012, 8(3): 406-417.
7. Pritzker KP, Gay S, Jimenez SA,et al. Osteoarthritis cartilage histopathology: grading and staging. Osteoarthritis Cartilage, 2006, 14(1): 13-29.
8. Veverka V, Henry AJ, Slocombe PM,et al. Characterization of the structural features and interactions of sclerostin: molecular insight into a key regulator of Wnt-mediated bone formation. J Biol Chem, 2009, 284(16): 10890-10900.
9. Wu L, Guo H, Sun K,et al. Sclerostin expression in the subchondral bone of patients with knee osteoarthritis. Int J Mol Med, 2016, 38(5): 1395-1402.
10. Kellgren JH, Lawrence JS. Radiological assessment of osteo-arthrosis. Ann Rheum Dis, 1957, 16(4): 494-502.
11. Yu DG, Nie SB, Liu FX,et al. Dynamic alterations in microarchitecture, mineralization and mechanical property of subchondral bone in rat medial meniscal tear model of osteoarthritis. Chin Med J (Engl), 2015, 128(21): 2879-2886.
12. Nevitt MC, Zhang Y, Javaid MK,et al. High systemic bone mineral density increases the risk of incident knee OA and joint space narrowing, but not radiographic progression of existing knee OA: the MOST study. Ann Rheum Dis, 2010, 69(1): 163-168.
13. Finnilä MA, Thevenot J, Aho OM,et al. Association between subchondral bone structure and osteoarthritis histopathological grade. J Orthop Res, 2016. [Epub ahead of print].
14. Compton JT, Lee FY. A review of osteocyte function and the emerging importance of sclerostin. J Bone Joint Surg (Am), 2014, 96(19): 1659-1668.
15. 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(9): 5866-5875.
16. Spatz JM, Wein MN, Gooi JH,et al. The Wnt inhibitor sclerostin is up-regulated by mechanical unloading in osteocytesin vitro. J Biol Chem, 2015, 290(27): 16744-16758.
17. Goldring SR. The osteocyte: key player in regulating bone turnover. RMD Open, 2015, 1(Suppl 1): e000049.
18. Chou CH, Wu CC, Song IW,et al. Genome-wide expression profiles of subchondral bone in osteoarthritis. Arthritis Res Ther, 2013, 15(6): R190.
19. Becker CB. Sclerostin inhibition for osteoporosis——a new approach. N Engl J Med, 2014, 370(5): 476-477.
20. MacNabb C, Patton D, Hayes JS. Sclerostin antibody therapy for the treatment of osteoporosis: Clinical prospects and challenges. J Osteoporos, 2016, 2016: 6217286.
21. Appelman-Dijkstra NM, Papapoulos SE. Sclerostin inhibition in the management of osteoporosis. Calcif Tissue Int, 2016, 98(4): 370-380.
22. Barr AJ, Campbell TM, Hopkinson D,et al. A systematic review of the relationship between subchondral bone features, pain and structural pathology in peripheral joint osteoarthritis. Arthritis Res Ther, 2015, 17(25): 228.

Chinese Journal of Reparative and Reconstructive Surgery

Expression of Sclerostin in medial and lateral subchondral bone of the varus osteoarthritic knee plateau

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