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Published in: Journal of Orthopaedic Surgery and Research 1/2019

Open Access 01-12-2019 | Knee Osteoarthritis | Research article

Identifying the role of ASPN and COMP genes in knee osteoarthritis development

Authors: Abhishek Mishra, Sachin Awasthi, Saloni Raj, Priya Mishra, Rajeshwar Nath Srivastava

Published in: Journal of Orthopaedic Surgery and Research | Issue 1/2019

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Abstract

Background

Osteoarthritis (OA) is a common cause of musculoskeletal disability among elders and is characterized by late-onset degeneration of articular cartilage. OA affects various joints, commonly hand, knee, and hip, with clinical features that are unique to each joint. This study was initiated to identify and evaluate the role of the ASPN and COMP genes in the development of knee OA.

Methods

A case–control study was carried out involving 500 cases with knee OA (diagnosed by the American College of Rheumatology) and an equal number of healthy controls. Blood was drawn for genomic DNA isolation. PCR-RFLP and TaqMan assay methods were used to identify the SNPs. mRNA and protein expression of genes were carried out in peripheral blood lymphocytes (PBLs) by RT-PCR and Western immunoblotting. The data obtained were analyzed for the statistical significance between control and case groups.

Results

The variant genotype of ASPN and COMP genes was found to be present at a relatively higher frequency in cases than controls. RT-PCR and immunochemical studies revealed increased mRNA and protein expression of such gene in PBLs isolated from cases of knee OA as compared to healthy control.

Conclusion

The allelic alteration in ASPN and COMP genes in knee OA cases points to the role of these genes in the development of knee OA. Further, increased mRNA and protein expression of ASPN and COMP in peripheral blood samples of patients with the disease suggest that expression profile of candidate gene could be used as a biomarker for predicting the development and progression of knee OA.
Literature
1.
go back to reference Sanghi D, Avasthi S, Mishra A, Singh A, Agarwal S, Srivastava RN. Is radiology a determinant of pain, stiffness, and functional disability in knee osteoarthritis? A cross-sectional study. J Orthop Sci. 2011;16(6):719–25 PubMed PMID: 21874334.CrossRef Sanghi D, Avasthi S, Mishra A, Singh A, Agarwal S, Srivastava RN. Is radiology a determinant of pain, stiffness, and functional disability in knee osteoarthritis? A cross-sectional study. J Orthop Sci. 2011;16(6):719–25 PubMed PMID: 21874334.CrossRef
2.
go back to reference Brandt KD, Dieppe P, Radin E. Etiopathogenesis of osteoarthritis. Med Clin North Am. 2009;93(1):1–24 xv. PubMed PMID: 19059018.PubMedCrossRef Brandt KD, Dieppe P, Radin E. Etiopathogenesis of osteoarthritis. Med Clin North Am. 2009;93(1):1–24 xv. PubMed PMID: 19059018.PubMedCrossRef
3.
go back to reference Spector TD, MacGregor AJ. Risk factors for osteoarthritis: genetics. Osteoarthritis Cartilage. 2004;12(Suppl A):S39–44 Osteoarthritis Research Society. PubMed PMID: 14698640.PubMedCrossRef Spector TD, MacGregor AJ. Risk factors for osteoarthritis: genetics. Osteoarthritis Cartilage. 2004;12(Suppl A):S39–44 Osteoarthritis Research Society. PubMed PMID: 14698640.PubMedCrossRef
4.
go back to reference Neogi T. The epidemiology and impact of pain in osteoarthritis. Osteoarthritis Cartilage. 2013;21(9):1145–53 Osteoarthritis Research Society. PubMed PMID: 23973124. eng.PubMedPubMedCentralCrossRef Neogi T. The epidemiology and impact of pain in osteoarthritis. Osteoarthritis Cartilage. 2013;21(9):1145–53 Osteoarthritis Research Society. PubMed PMID: 23973124. eng.PubMedPubMedCentralCrossRef
5.
go back to reference Fukutani N, Iijima H, Aoyama T, Yamamoto Y, Hiraoka M, Miyanobu K, et al. Knee pain during activities of daily living and its relationship with physical activity in patients with early and severe knee osteoarthritis. Clin Rheumatol. 2016;35(9):2307–16 PubMed PMID: 27041381. eng.PubMedCrossRef Fukutani N, Iijima H, Aoyama T, Yamamoto Y, Hiraoka M, Miyanobu K, et al. Knee pain during activities of daily living and its relationship with physical activity in patients with early and severe knee osteoarthritis. Clin Rheumatol. 2016;35(9):2307–16 PubMed PMID: 27041381. eng.PubMedCrossRef
6.
go back to reference Valdes AM, Spector TD. The contribution of genes to osteoarthritis. Med Clin North Am. 2009;93(1):45–66 x. PubMed PMID: 19059021.PubMedCrossRef Valdes AM, Spector TD. The contribution of genes to osteoarthritis. Med Clin North Am. 2009;93(1):45–66 x. PubMed PMID: 19059021.PubMedCrossRef
7.
go back to reference Valdes AM, Loughlin J, Oene MV, Chapman K, Surdulescu GL, Doherty M, 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(1):137–46 PubMed PMID: 17195216.PubMedCrossRef Valdes AM, Loughlin J, Oene MV, Chapman K, Surdulescu GL, Doherty M, 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(1):137–46 PubMed PMID: 17195216.PubMedCrossRef
8.
go back to reference Mabuchi A, Ikeda T, Fukuda A, Koshizuka Y, Hiraoka H, Miyoshi K, et al. Identification of sequence polymorphisms of the COMP (cartilage oligomeric matrix protein) gene and association study in osteoarthrosis of the knee and hip joints. J Hum Genet. 2001;46(8):456–62 PubMed PMID: 11501943. eng.PubMedCrossRef Mabuchi A, Ikeda T, Fukuda A, Koshizuka Y, Hiraoka H, Miyoshi K, et al. Identification of sequence polymorphisms of the COMP (cartilage oligomeric matrix protein) gene and association study in osteoarthrosis of the knee and hip joints. J Hum Genet. 2001;46(8):456–62 PubMed PMID: 11501943. eng.PubMedCrossRef
9.
go back to reference Song YQ, Cheung KM, Ho DW, Poon SC, Chiba K, Kawaguchi Y, et al. Association of the asporin D14 allele with lumbar-disc degeneration in Asians. Am J Hum Genet. 2008;82(3):744–7 PubMed PMID: 18304494. eng.PubMedPubMedCentralCrossRef Song YQ, Cheung KM, Ho DW, Poon SC, Chiba K, Kawaguchi Y, et al. Association of the asporin D14 allele with lumbar-disc degeneration in Asians. Am J Hum Genet. 2008;82(3):744–7 PubMed PMID: 18304494. eng.PubMedPubMedCentralCrossRef
10.
go back to reference Sakao K, Takahashi KA, Arai Y, Saito M, Honjyo K, Hiraoka N, et al. Asporin and transforming growth factor-beta gene expression in osteoblasts from subchondral bone and osteophytes in osteoarthritis. J Orthop Sci. 2009;14(6):738–47 PubMed PMID: 19997821. eng.PubMedCrossRef Sakao K, Takahashi KA, Arai Y, Saito M, Honjyo K, Hiraoka N, et al. Asporin and transforming growth factor-beta gene expression in osteoblasts from subchondral bone and osteophytes in osteoarthritis. J Orthop Sci. 2009;14(6):738–47 PubMed PMID: 19997821. eng.PubMedCrossRef
11.
go back to reference Kizawa H, Kou I, Iida A, Sudo A, Miyamoto Y, Fukuda A, et al. An aspartic acid repeat polymorphism in asporin inhibits chondrogenesis and increases susceptibility to osteoarthritis. Nat Genet. 2005;37(2):138–44 PubMed PMID: 15640800.PubMedCrossRef Kizawa H, Kou I, Iida A, Sudo A, Miyamoto Y, Fukuda A, et al. An aspartic acid repeat polymorphism in asporin inhibits chondrogenesis and increases susceptibility to osteoarthritis. Nat Genet. 2005;37(2):138–44 PubMed PMID: 15640800.PubMedCrossRef
12.
go back to reference Mabuchi A, Manabe N, Haga N, Kitoh H, Ikeda T, Kawaji H, et al. Novel types of COMP mutations and genotype-phenotype association in pseudoachondroplasia and multiple epiphyseal dysplasia. Hum Genet. 2003;112(1):84–90 PubMed PMID: 12483304.PubMedCrossRef Mabuchi A, Manabe N, Haga N, Kitoh H, Ikeda T, Kawaji H, et al. Novel types of COMP mutations and genotype-phenotype association in pseudoachondroplasia and multiple epiphyseal dysplasia. Hum Genet. 2003;112(1):84–90 PubMed PMID: 12483304.PubMedCrossRef
13.
go back to reference Chen FH, Herndon ME, Patel N, Hecht JT, Tuan RS, Lawler J. Interaction of cartilage oligomeric matrix protein/thrombospondin 5 with aggrecan. J Biol Chem. 2007;282(34):24591–8 PubMed PMID: 17588949. eng.PubMedPubMedCentralCrossRef Chen FH, Herndon ME, Patel N, Hecht JT, Tuan RS, Lawler J. Interaction of cartilage oligomeric matrix protein/thrombospondin 5 with aggrecan. J Biol Chem. 2007;282(34):24591–8 PubMed PMID: 17588949. eng.PubMedPubMedCentralCrossRef
14.
go back to reference Posey KL, Hecht JT. The role of cartilage oligomeric matrix protein (COMP) in skeletal disease. Curr Drug Targets. 2008;9(10):869–77 PubMed PMID: 18855621. eng.PubMedCrossRef Posey KL, Hecht JT. The role of cartilage oligomeric matrix protein (COMP) in skeletal disease. Curr Drug Targets. 2008;9(10):869–77 PubMed PMID: 18855621. eng.PubMedCrossRef
15.
go back to reference Mishra A, Sanghi D, Sharma AC, Raj S, Maurya SS, Avasthi S, et al. Association of polymorphism in growth and differentiation factor 5 gene with osteoarthritis knee. Am J Biochem Biotechnol. 2013;9(1):1–7.CrossRef Mishra A, Sanghi D, Sharma AC, Raj S, Maurya SS, Avasthi S, et al. Association of polymorphism in growth and differentiation factor 5 gene with osteoarthritis knee. Am J Biochem Biotechnol. 2013;9(1):1–7.CrossRef
16.
go back to reference Neidhart M, Muller-Ladner U, Frey W, Bosserhoff AK, Colombani PC, Frey-Rindova P, et al. Increased serum levels of non-collagenous matrix proteins (cartilage oligomeric matrix protein and melanoma inhibitory activity) in marathon runners. Osteoarthritis Cartilage. 2000;8(3):222–9 Osteoarthritis Research Society. PubMed PMID: 10806050. eng.PubMedCrossRef Neidhart M, Muller-Ladner U, Frey W, Bosserhoff AK, Colombani PC, Frey-Rindova P, et al. Increased serum levels of non-collagenous matrix proteins (cartilage oligomeric matrix protein and melanoma inhibitory activity) in marathon runners. Osteoarthritis Cartilage. 2000;8(3):222–9 Osteoarthritis Research Society. PubMed PMID: 10806050. eng.PubMedCrossRef
17.
go back to reference Mishra A, Srivastava RN, Awasthi S, Parmar D, Mishra P. Expression of genes and their polymorphism influences the risk of knee osteoarthritis. J Nucleic Acids. 2017;2017:3138254 PubMed PMID: 29129999. Pubmed Central PMCID: 5654253.PubMedPubMedCentralCrossRef Mishra A, Srivastava RN, Awasthi S, Parmar D, Mishra P. Expression of genes and their polymorphism influences the risk of knee osteoarthritis. J Nucleic Acids. 2017;2017:3138254 PubMed PMID: 29129999. Pubmed Central PMCID: 5654253.PubMedPubMedCentralCrossRef
18.
go back to reference Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987;162(1):156–9 PubMed PMID: 2440339. eng.PubMedCrossRef Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987;162(1):156–9 PubMed PMID: 2440339. eng.PubMedCrossRef
19.
go back to reference Dey A, Parmar D, Dayal M, Dhawan A, Seth PK. Cytochrome P450 1A1 (CYP1A1) in blood lymphocytes evidence for catalytic activity and mRNA expression. Life sciences. 2001;69(4):383–93 PubMed PMID: 11459429. eng.PubMedCrossRef Dey A, Parmar D, Dayal M, Dhawan A, Seth PK. Cytochrome P450 1A1 (CYP1A1) in blood lymphocytes evidence for catalytic activity and mRNA expression. Life sciences. 2001;69(4):383–93 PubMed PMID: 11459429. eng.PubMedCrossRef
20.
go back to reference Shah PP, Saurabh K, Pant MC, Mathur N, Parmar D. Evidence for increased cytochrome P450 1A1 expression in blood lymphocytes of lung cancer patients. Mutat Res. 2009;670(1–2):74–8 PubMed PMID: 19632247. eng.PubMedCrossRef Shah PP, Saurabh K, Pant MC, Mathur N, Parmar D. Evidence for increased cytochrome P450 1A1 expression in blood lymphocytes of lung cancer patients. Mutat Res. 2009;670(1–2):74–8 PubMed PMID: 19632247. eng.PubMedCrossRef
21.
go back to reference Juchtmans N, Dhollander AA, Coudenys J, Audenaert EA, Pattyn C, Lambrecht S, et al. Distinct dysregulation of the small leucine-rich repeat protein family in osteoarthritic acetabular labrum compared to articular cartilage. Arthritis Rheumatol. 2015;67(2):435–41 PubMed PMID: 25371314. Epub 2014/11/06. eng.PubMedCrossRef Juchtmans N, Dhollander AA, Coudenys J, Audenaert EA, Pattyn C, Lambrecht S, et al. Distinct dysregulation of the small leucine-rich repeat protein family in osteoarthritic acetabular labrum compared to articular cartilage. Arthritis Rheumatol. 2015;67(2):435–41 PubMed PMID: 25371314. Epub 2014/11/06. eng.PubMedCrossRef
22.
go back to reference Bhagwat SR, Chandrashekar DS, Kakar R, Davuluri S, Bajpai AK, Nayak S, et al. Endometrial receptivity: a revisit to functional genomics studies on human endometrium and creation of HGEx-ERdb. PLoS One. 2013;8(3):e58419 PubMed PMID: 23555582. Pubmed Central PMCID: PMC3608645. Epub 2013/04/05. eng.PubMedPubMedCentralCrossRef Bhagwat SR, Chandrashekar DS, Kakar R, Davuluri S, Bajpai AK, Nayak S, et al. Endometrial receptivity: a revisit to functional genomics studies on human endometrium and creation of HGEx-ERdb. PLoS One. 2013;8(3):e58419 PubMed PMID: 23555582. Pubmed Central PMCID: PMC3608645. Epub 2013/04/05. eng.PubMedPubMedCentralCrossRef
23.
go back to reference Ikegawa S, Ohashi H, Nishimura G, Kim KC, Sannohe A, Kimizuka M, et al. Novel and recurrent COMP (cartilage oligomeric matrix protein) mutations in pseudoachondroplasia and multiple epiphyseal dysplasia. Hum Genet. 1998;103(6):633–8 PubMed PMID: 9921895. eng.PubMedCrossRef Ikegawa S, Ohashi H, Nishimura G, Kim KC, Sannohe A, Kimizuka M, et al. Novel and recurrent COMP (cartilage oligomeric matrix protein) mutations in pseudoachondroplasia and multiple epiphyseal dysplasia. Hum Genet. 1998;103(6):633–8 PubMed PMID: 9921895. eng.PubMedCrossRef
24.
go back to reference Kaliakatsos M, Tzetis M, Kanavakis E, Fytili P, Chouliaras G, Karachalios T, et al. Asporin and knee osteoarthritis in patients of Greek origin. Osteoarthritis Cartilage. 2006;14(6):609–11 Osteoarthritis Research Society. PubMed PMID: 16377215. eng.PubMedCrossRef Kaliakatsos M, Tzetis M, Kanavakis E, Fytili P, Chouliaras G, Karachalios T, et al. Asporin and knee osteoarthritis in patients of Greek origin. Osteoarthritis Cartilage. 2006;14(6):609–11 Osteoarthritis Research Society. PubMed PMID: 16377215. eng.PubMedCrossRef
25.
go back to reference Shi D, Dai J, Zhu P, Qin J, Zhu L, Zhu H, et al. Association of the D repeat polymorphism in the ASPN gene with developmental dysplasia of the hip: a case-control study in Han Chinese. Arthritis Res Ther. 2011;13(1):R27 PubMed PMID: 21329514. eng.PubMedPubMedCentralCrossRef Shi D, Dai J, Zhu P, Qin J, Zhu L, Zhu H, et al. Association of the D repeat polymorphism in the ASPN gene with developmental dysplasia of the hip: a case-control study in Han Chinese. Arthritis Res Ther. 2011;13(1):R27 PubMed PMID: 21329514. eng.PubMedPubMedCentralCrossRef
26.
go back to reference Chen TL, Posey KL, Hecht JT, Vertel BM. COMP mutations: domain-dependent relationship between abnormal chondrocyte trafficking and clinical PSACH and MED phenotypes. J Cell Biochem. 2008;103(3):778–87 PubMed PMID: 17570134. eng.PubMedCrossRef Chen TL, Posey KL, Hecht JT, Vertel BM. COMP mutations: domain-dependent relationship between abnormal chondrocyte trafficking and clinical PSACH and MED phenotypes. J Cell Biochem. 2008;103(3):778–87 PubMed PMID: 17570134. eng.PubMedCrossRef
27.
go back to reference Briggs MD, Mortier GR, Cole WG, King LM, Golik SS, Bonaventure J, et al. Diverse mutations in the gene for cartilage oligomeric matrix protein in the pseudoachondroplasia-multiple epiphyseal dysplasia disease spectrum. Am J Hum Genet. 1998;62(2):311–9 PubMed PMID: 9463320. eng.PubMedPubMedCentralCrossRef Briggs MD, Mortier GR, Cole WG, King LM, Golik SS, Bonaventure J, et al. Diverse mutations in the gene for cartilage oligomeric matrix protein in the pseudoachondroplasia-multiple epiphyseal dysplasia disease spectrum. Am J Hum Genet. 1998;62(2):311–9 PubMed PMID: 9463320. eng.PubMedPubMedCentralCrossRef
Metadata
Title
Identifying the role of ASPN and COMP genes in knee osteoarthritis development
Authors
Abhishek Mishra
Sachin Awasthi
Saloni Raj
Priya Mishra
Rajeshwar Nath Srivastava
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Journal of Orthopaedic Surgery and Research / Issue 1/2019
Electronic ISSN: 1749-799X
DOI
https://doi.org/10.1186/s13018-019-1391-7

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