Chondromodulin‑I expression and correlation with angiogenesis in human osteoarthritic cartilage

Deng,Bing; Chen,Cheng; Gong,Xiaoyuan; Guo,Lin; Chen,Hao; Yin,Li; Yang,Liu; Wang,Fuyou

doi:10.3892/mmr.2017.6775

Chondromodulin‑I expression and correlation with angiogenesis in human osteoarthritic cartilage

Authors:
- Bing Deng
- Cheng Chen
- Xiaoyuan Gong
- Lin Guo
- Hao Chen
- Li Yin
- Liu Yang
- Fuyou Wang
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Affiliations: Center for Joint Surgery, Southwest Hospital, The Third Military Medical University, Chongqing 400038, P.R. China
Published online on: June 14, 2017 https://doi.org/10.3892/mmr.2017.6775
Pages: 2142-2148

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Abstract

The present study aimed to evaluate the expression and localization of chondromodulin‑I (ChM‑I) in human osteoarthritic cartilage and its correlation with vascular invasion during osteoarthritis (OA) progression. Osteochondral specimens were collected from patients with OA, as well as from young and aged donors without joint diseases. The grade and the number of vascular channels terminating in non‑calcified cartilage of these collected specimens were assessed by Safranin‑O/Fast green staining. ChM‑I expression in articular cartilage was examined by immunohistochemistry, western blotting and reverse transcription‑quantitative polymerase chain reaction analyses. ChM‑I protein and mRNA levels in articular cartilage appeared to be consistent between the normal young and aged groups (P>0.05). In mildly degenerated cartilage, ChM‑I expression decreased in the extracellular matrix (ECM) of the superficial zone and in the cytoplasm of the superficial and middle zone compared with normal cartilage (P<0.05). In moderately degenerated cartilage, ChM‑I protein expression was reduced in the ECM of all zones of articular cartilage, but the immunostaining intensity in the cytoplasm was increased. In severely degenerated cartilage, ChM‑I expression was detected primarily in the cytoplasm of the cluster‑forming chondrocytes. The density of vascular channels was correlated with the ChM‑I expression levels in cartilage ECM. ChM‑I expression was reduced in OA cartilage matrix, compared with normal cartilage (both young and aged), and correlated with angiogenesis, indicating that loss of ChM‑I may promote angiogenesis in OA cartilage. Expression of ChM‑I protein in the cytoplasm was decreased in mildly degenerated cartilage, whereas ChM‑I expression increased in moderately degenerated cartilage accompanied by chondrocyte proliferation. These findings suggested that attenuation of ChM‑I in the cartilage ECM may be due to decreased expression of ChM‑I in cytoplasm of early stage OA and increased depletion of ChM‑I in the ECM of advanced stage OA.

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1	Ashraf S and Walsh DA: Angiogenesis in osteoarthritis. Curr Opin Rheumatol. 20:573–580. 2008. View Article : Google Scholar : PubMed/NCBI
2	Suri S and Walsh DA: Osteochondral alterations in osteoarthritis. Bone. 51:204–211. 2012. View Article : Google Scholar : PubMed/NCBI
3	Walsh DA, McWilliams DF, Turley MJ, Dixon MR, Fransès RE, Mapp PI and Wilson D: Angiogenesis and nerve growth factor at the osteochondral junction in rheumatoid arthritis and osteoarthritis. Rheumatology (Oxford). 49:1852–1861. 2010. View Article : Google Scholar : PubMed/NCBI
4	Hiraki Y, Tanaka H, Inoue H, Kondo J, Kamizono A and Suzuki F: Molecular cloning of a new class of cartilage-specific matrix, chondromodulin-I, which stimulates growth of cultured chondrocytes. Biochem Biophys Res Commun. 175:971–977. 1991. View Article : Google Scholar : PubMed/NCBI
5	Hiraki Y, Inoue H, Iyama K, Kamizono A, Ochiai M, Shukunami C, Iijima S, Suzuki F and Kondo J: Identification of chondromodulin I as a novel endothelial cell growth inhibitor. Purification and its localization in the avascular zone of epiphyseal cartilage. J Biol Chem. 272:32419–32426. 1997. View Article : Google Scholar : PubMed/NCBI
6	Shukunami C, Iyama K, Inoue H and Hiraki Y: Spatiotemporal pattern of the mouse chondromodulin-I gene expression and its regulatory role in vascular invasion into cartilage during endochondral bone formation. Int J Dev Biol. 43:39–49. 1999.PubMed/NCBI
7	Kusafuka K, Hiraki Y, Shukunami C, Yamaguchi A, Kayano T and Takemura T: Cartilage-specific matrix protein chondromodulin-I is associated with chondroid formation in salivary pleomorphic adenomas: Immunohistochemical analysis. Am J Pathol. 158:1465–1472. 2001. View Article : Google Scholar : PubMed/NCBI
8	Miura S, Mitsui K, Heishi T, Shukunami C, Sekiguchi K, Kondo J, Sato Y and Hiraki Y: Impairment of VEGF-A-stimulated lamellipodial extensions and motility of vascular endothelial cells by chondromodulin-I, a cartilage-derived angiogenesis inhibitor. Exp Cell Res. 316:775–788. 2010. View Article : Google Scholar : PubMed/NCBI
9	Shukunami C and Hiraki Y: Role of cartilage-derived anti-angiogenic factor, chondromodulin-I, during endochondral bone formation. Osteoarthritis Cartilage. 9 Suppl A:S91–S101. 2001. View Article : Google Scholar : PubMed/NCBI
10	Kusafuka K, Hiraki Y, Shukunami C, Kayano T and Takemura T: Cartilage-specific matrix protein, chondromodulin-I (ChM-I), is a strong angio-inhibitor in endochondral ossification of human neonatal vertebral tissues in vivo: Relationship with angiogenic factors in the cartilage. Acta Histochem. 104:167–175. 2002. View Article : Google Scholar : PubMed/NCBI
11	Hayami T, Funaki H, Yaoeda K, Mitui K, Yamagiwa H, Tokunaga K, Hatano H, Kondo J, Hiraki Y, Yamamoto T, et al: Expression of the cartilage derived anti-angiogenic factor chondromodulin-I decreases in the early stage of experimental osteoarthritis. J Rheumatol. 30:2207–2217. 2003.PubMed/NCBI
12	Sakamoto J, Origuchi T, Okita M, Nakano J, Kato K, Yoshimura T, Izumi S, Komori T, Nakamura H, Ida H, et al: Immobilization-induced cartilage degeneration mediated through expression of hypoxia-inducible factor-1alpha, vascular endothelial growth factor, and chondromodulin-I. Connect Tissue Res. 50:37–45. 2009. View Article : Google Scholar : PubMed/NCBI
13	Wang QY, Dai J, Kuang B, Zhang J, Yu SB, Duan YZ and Wang MQ: Osteochondral angiogenesis in rat mandibular condyles with osteoarthritis-like changes. Arch Oral Biol. 57:620–629. 2012. View Article : Google Scholar : PubMed/NCBI
14	Pritzker KP, Gay S, Jimenez SA, Ostergaard K, Pelletier JP, Revell PA, Salter D and van den Berg WB: Osteoarthritis cartilage histopathology: Grading and staging. Osteoarthritis Cartilage. 14:13–29. 2006. View Article : Google Scholar : PubMed/NCBI
15	Fransès RE, McWilliams DF, Mapp PI and Walsh DA: Osteochondral angiogenesis and increased protease inhibitor expression in OA. Osteoarthritis Cartilage. 18:563–571. 2010. View Article : Google Scholar : PubMed/NCBI
16	Livak KJ and Schmittgen TD: Analysis of gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
17	Fang W, Friis TE, Long X and Xiao Y: Expression of chondromodulin-1 in the temporomandibular joint condylar cartilage and disc. J Oral Pathol Med. 39:356–360. 2010.PubMed/NCBI
18	Patra D and Sandell LJ: Antiangiogenic and anticancer molecules in cartilage. Expert Rev Mol Med. 14:e102012. View Article : Google Scholar : PubMed/NCBI
19	Xing S, Wang Z, Xi H, Zhou L, Wang D, Sang L, Wang X, Qi M and Zhai L: Establishment of rat bone mesenchymal stem cell lines stably expressing Chondromodulin I. Int J Clin Exp Med. 5:34–43. 2012.PubMed/NCBI
20	Pauli C, Whiteside R, Heras FL, Nesic D, Koziol J, Grogan SP, Matyas J, Pritzker KP, D'Lima DD and Lotz MK: Comparison of cartilage histopathology assessment systems on human knee joints at all stages of osteoarthritis development. Osteoarthritis Cartilage. 20:476–485. 2012. View Article : Google Scholar : PubMed/NCBI
21	Mononen ME, Mikkola MT, Julkunen P, Ojala R, Nieminen MT, Jurvelin JS and Korhonen RK: Effect of superficial collagen patterns and fibrillation of femoral articular cartilage on knee joint mechanics-a 3D finite element analysis. J Biomech. 45:579–587. 2012. View Article : Google Scholar : PubMed/NCBI
22	Tardif G, Pelletier JP, Boileau C and Martel-Pelletier J: The BMP antagonists follistatin and gremlin in normal and early osteoarthritic cartilage: An immunohistochemical study. Osteoarthritis Cartilage. 17:263–270. 2009. View Article : Google Scholar : PubMed/NCBI
23	Guo J, Zhang W, Li Q, Gan H and Wang Z: Significance of expressions of matrix metalloproteinase 9 mRNA, transforming growth factor beta1, mRNA and corresponding proteins in osteoarthritis. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 25:992–997. 2011.(In Chinese). PubMed/NCBI
24	Shukunami C and Hiraki Y: Expression of cartilage-specific functional matrix chondromodulin-I mRNA in rabbit growth plate chondrocytes and its responsiveness to growth stimuli in vitro. Biochem Biophys Res Commun. 249:885–890. 1998. View Article : Google Scholar : PubMed/NCBI
25	Hiraki Y, Inoue H, Kondo J, Kamizono A, Yoshitake Y, Shukunami C and Suzuki F: A novel growth-promoting factor derived from fetal bovine cartilage, chondromodulin II Purification and amino acid sequence. J Biol Chem. 271:22657–22662. 1996. View Article : Google Scholar : PubMed/NCBI
26	Levick JR: Hypoxia and acidosis in chronic inflammatory arthritis; relation to vascular supply and dynamic effusion pressure. J Rheumatol. 17:579–582. 1990.PubMed/NCBI
27	Biniecka M, Kennedy A, Fearon U, Ng CT, Veale DJ and O'Sullivan JN: Oxidative damage in synovial tissue is associated with in vivo hypoxic status in the arthritic joint. Ann Rheum Dis. 69:1172–1178. 2010. View Article : Google Scholar : PubMed/NCBI
28	Lafont JE, Talma S, Hopfgarten C and Murphy CL: Hypoxia promotes the differentiated human articular chondrocyte phenotype through SOX9-dependent and -independent pathways. J Biol Chem. 283:4778–4786. 2008. View Article : Google Scholar : PubMed/NCBI
29	Takao T, Iwaki T, Kondo J and Hiraki Y: Immunohistochemistry of chondromodulin-I in the human intervertebral discs with special reference to the degenerative changes. Histochem J. 32:545–550. 2000. View Article : Google Scholar : PubMed/NCBI
30	Azizan A, Holaday N and Neame PJ: Post-translational processing of bovine chondromodulin-I. J Biol Chem. 276:23632–23638. 2001. View Article : Google Scholar : PubMed/NCBI
31	Miura S, Kondo J, Takimoto A, Sano-Takai H, Guo L, Shukunami C, Tanaka H and Hiraki Y: The N-terminal cleavage of chondromodulin-I in growth-plate cartilage at the hypertrophic and calcified zones during bone development. PLoS One. 9:e942392014. View Article : Google Scholar : PubMed/NCBI
32	Barbero A, Grogan S, Schäfer D, Heberer M, Mainil-Varlet P and Martin I: Age related changes in human articular chondrocyte yield, proliferation and post-expansion chondrogenic capacity. Osteoarthritis Cartilage. 12:476–484. 2004. View Article : Google Scholar : PubMed/NCBI
33	Fransès RE, McWilliams DF, Mapp PI and Walsh DA: Osteochondral angiogenesis and increased protease inhibitor expression in OA. Osteoarthritis Cartilage. 18:563–571. 2010. View Article : Google Scholar : PubMed/NCBI