EXPRESSIONS OF CARTILAGE DEGENERATIVE RELATED GENES AND microRNAs IN TORN MENISCUS_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

LONGYi ,  HEAishan , ZHANGZhiqi , MENGFangang , HOUChanghe , ZHANGZiji , HUANGGuangxin , LIAOWeiming

Department of Joint Surgery, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou Guangdong, 510080, P. R. China;

Corresponding author：

HEAishan, Email: heaishan2006@139.com

Keywords：

Meniscal tears; Osteoarthritis; Cartilage degenerative related genes; microRNAs

DOI：

10.7507/1002-1892.20150065

Video：

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Objective To investigate the expressions of cartilage degenerative related genes in meniscus, and to evaluate the potential effect of meniscal damage on cartilage degeneration, and to analyze the relationship between microRNAs (miRNAs) expression and cartilage degeneration. Methods Meniscal tissue was collected from 5 patients undergoing partial meniscectomy between September 2012 and October 2013 (experimental group), and normally meniscal tissue without tearing from amputees was used as controls (control group). Pathological changes of menisci were observed; and real-time fluorescent quatitative PCR was performed to examine the relative expression levels of cartilage degenerative related genes and miRNAs:Aggrecan (ACAN), type X collagen (COL10A1), matrix metalloproteinases 13 (MMP-13), CCAAT enhancer binding protein β (CEBP-β), a disintegrin and metalloproteinase with thrombospondinmotif 5 (ADAMTS-5), miR-193b, miR-92a, and miR-455-3p in meniscus. Results There were varying degrees of degenerative pathological changes in torn meniscus of experimental group. Compared with normal meniscus of control group, the expression of ACAN was decreased, while the expressions of COL10A1, CEBP-β, ADAMTS-5, and MMP-13 were increased in torn meniscus of experimental group; and significant difference was found (P<0.05) except ACAN and MMP-13 (P>0.05). The expressions of miR-92a, miR-455-3p, and miR-193b in torn meniscus of experimental group were significantly higher than those in normal meniscus of control group (P<0.05). Conclusion Meniscal tissue has the intrinsic tendency of degeration after meniscus tear. The torn meniscus has greater stimulative impact on cartilage degeneration than normally morphological meniscus without tearing. The cartilage degenerative related miRNAs, including miR-193b, miR-92a, and miR-455-3p may contribute to the up-regulation of osteoarthritis.

Citation： LONGYi, HEAishan, ZHANGZhiqi, MENGFangang, HOUChanghe, ZHANGZiji, HUANGGuangxin, LIAOWeiming. EXPRESSIONS OF CARTILAGE DEGENERATIVE RELATED GENES AND microRNAs IN TORN MENISCUS. Chinese Journal of Reparative and Reconstructive Surgery, 2015, 29(3): 301-306. doi: 10.7507/1002-1892.20150065 Copy

1.	Samuels J, Krasnokutsky S, Abramson SB. Osteoarthritis:a tale of three tissues. Bull NYU Hosp Jt Dis, 2008, 66(3):244-250.
2.	Sun Y, Mauerhan DR, Honeycutt PR, et al. Analysis of meniscal degeneration and meniscal gene expression. BMC Musculoskelet Disord, 2010, 11:19.
3.	Englund M, Guermazi A, Lohmander SL. The role of the meniscus in knee osteoarthritis:a cause or consequence? Radiol Clin North Am, 2009, 47(4):703-712.
4.	Maldonado M, Nam J. The role of changes in extracellular matrix of cartilage in the presence of inflammation on the pathology of osteoarthritis. Biomed Res Int, 2013, 2013:284873.
5.	Englund M, Roemer FW, Hayashi D, et al. Meniscus pathology, osteoarthritis and the treatment controversy. Nat Rev Rheumatol, 2012, 8(7):412-419.
6.	Chang A, Moisio K, Chmiel JS, et al. Subregional effects of meniscal tears on cartilage loss over 2 years in knee osteoarthritis. Ann Rheum Dis, 2011, 70(1):74-79.
7.	Laible C, Stein DA, Kiridly DN. Meniscal repair. J Am Acad Orthop Surg, 2013, 21(4):204-213.
8.	李国军, 李康华, 朱勇, 等. 兔前交叉韧带断裂后外侧半月板的组织学退变. 中国组织工程研究与临床康复, 2009, 13(20):3873-3876.
9.	Okubo M, Okada Y. Destruction of the articular cartilage in osteoarthritis. Clin Calcium, 2013, 23(12):1705-1713.
10.	Chia SL, Sawaji Y, Burleigh A, et al. Fibroblast growth factor 2 is an intrinsic chondroprotective agent that suppresses ADAMTS-5 and delays cartilage degradation in murine osteoarthritis. Arthritis Rheum, 2009, 60(7):2019-2027.
11.	Linsenmayer TF, Long F, Nurminskaya M, et al. Type X collagen and other up-regulated components of the avian hypertrophic cartilage program. Prog Nucleic Acid Res Mol Biol, 1998, 60:79-109.
12.	Shen G. The role of type X collagen in facilitating and regulating endochondral ossification of articular cartilage. Orthod Craniofac Res, 2005, 8(1):11-17.
13.	Hirata M, Kugimiya F, Fukai A, et al. C/EBPbeta promotes transition from proliferation to hypertrophic differentiation of chondrocytes through transactivation of p57. PLoS One, 2009, 4(2):e4543.
14.	Tsushima H, Okazaki K, Hayashida M. CCAAT/enhancer binding protein β regulates expression of matrix metalloproteinase-3 in arthritis. Ann Rheum Dis, 2012, 71(1):99-107.
15.	HayashidaM, Okazaki K, Fukushi J. CCAAT/enhancer binding protein beta mediates expression of matrix metalloproteinase 13 in human articular chondrocytes in inflammatory arthritis. Arthritis Rheum, 2009, 60(3):708-716.
16.	Hirata M, Kugimiya F, Fukai A, et al. C/EBPβ and RUNX2 cooperate to degrade cartilage with MMP-13 as the target and HIF-2α as the inducer in chondrocytes. Hum Mol Genet, 2012, 21(5):1111-1123.
17.	Englund M, Guermazi A, Roemer FW, et al. Meniscal tear in knees without surgery and the development of radiographic osteoarthritis among middle-aged and elderly persons:the multicenter osteoarthritis study. Arthritis Rheum, 2009, 60(3):831-839.
18.	Carthew RW, Sontheimer EJ. Origins and mechanisms of miRNAs and siRNAs. Cell, 2009, 136(4):642-655.
19.	Zhang Z, Kang Y, Zhang Z, et al. Expression of microRNAs during chondrogenesis of human adipose-derived stem cells. Osteoarthritis Cartilage, 2012, 20(12):1638-1646.
20.	Ukai T, Sato M, Akutsu H, et al. MicroRNA-199a-3p, microRNA-193b, and microRNA-320c are correlated to aging and regulate human cartilage metabolism. J Orthop Res, 2012, 30(12):1915-1922.
21.	Swingler TE, Wheeler G, Carmont V, et al. The expression and function of microRNAs in chondrogenesis and osteoarthritis. Arthritis Rheum, 2012, 64(6):1909-1919.
22.	BrophyRH, Rai MF, Zhang Z, et al. Molecular analysis of age and sex-related gene expression in meniscal tears with and without a concomitant anterior cruciate ligament tear. J Bone Joint Surg (Am), 2012, 94(5):385-393.
23.	Henry S, Mascarenhas R, Kowalchuk D, et al. Medial meniscus tear morphology and chondral degeneration of the knee:is there a relationship? Arthroscopy, 2012, 28(8):1124-1134.e2.

1. Samuels J, Krasnokutsky S, Abramson SB. Osteoarthritis:a tale of three tissues. Bull NYU Hosp Jt Dis, 2008, 66(3):244-250.
2. Sun Y, Mauerhan DR, Honeycutt PR, et al. Analysis of meniscal degeneration and meniscal gene expression. BMC Musculoskelet Disord, 2010, 11:19.
3. Englund M, Guermazi A, Lohmander SL. The role of the meniscus in knee osteoarthritis:a cause or consequence? Radiol Clin North Am, 2009, 47(4):703-712.
4. Maldonado M, Nam J. The role of changes in extracellular matrix of cartilage in the presence of inflammation on the pathology of osteoarthritis. Biomed Res Int, 2013, 2013:284873.
5. Englund M, Roemer FW, Hayashi D, et al. Meniscus pathology, osteoarthritis and the treatment controversy. Nat Rev Rheumatol, 2012, 8(7):412-419.
6. Chang A, Moisio K, Chmiel JS, et al. Subregional effects of meniscal tears on cartilage loss over 2 years in knee osteoarthritis. Ann Rheum Dis, 2011, 70(1):74-79.
7. Laible C, Stein DA, Kiridly DN. Meniscal repair. J Am Acad Orthop Surg, 2013, 21(4):204-213.
8. 李国军, 李康华, 朱勇, 等. 兔前交叉韧带断裂后外侧半月板的组织学退变. 中国组织工程研究与临床康复, 2009, 13(20):3873-3876.
9. Okubo M, Okada Y. Destruction of the articular cartilage in osteoarthritis. Clin Calcium, 2013, 23(12):1705-1713.
10. Chia SL, Sawaji Y, Burleigh A, et al. Fibroblast growth factor 2 is an intrinsic chondroprotective agent that suppresses ADAMTS-5 and delays cartilage degradation in murine osteoarthritis. Arthritis Rheum, 2009, 60(7):2019-2027.
11. Linsenmayer TF, Long F, Nurminskaya M, et al. Type X collagen and other up-regulated components of the avian hypertrophic cartilage program. Prog Nucleic Acid Res Mol Biol, 1998, 60:79-109.
12. Shen G. The role of type X collagen in facilitating and regulating endochondral ossification of articular cartilage. Orthod Craniofac Res, 2005, 8(1):11-17.
13. Hirata M, Kugimiya F, Fukai A, et al. C/EBPbeta promotes transition from proliferation to hypertrophic differentiation of chondrocytes through transactivation of p57. PLoS One, 2009, 4(2):e4543.
14. Tsushima H, Okazaki K, Hayashida M. CCAAT/enhancer binding protein β regulates expression of matrix metalloproteinase-3 in arthritis. Ann Rheum Dis, 2012, 71(1):99-107.
15. HayashidaM, Okazaki K, Fukushi J. CCAAT/enhancer binding protein beta mediates expression of matrix metalloproteinase 13 in human articular chondrocytes in inflammatory arthritis. Arthritis Rheum, 2009, 60(3):708-716.
16. Hirata M, Kugimiya F, Fukai A, et al. C/EBPβ and RUNX2 cooperate to degrade cartilage with MMP-13 as the target and HIF-2α as the inducer in chondrocytes. Hum Mol Genet, 2012, 21(5):1111-1123.
17. Englund M, Guermazi A, Roemer FW, et al. Meniscal tear in knees without surgery and the development of radiographic osteoarthritis among middle-aged and elderly persons:the multicenter osteoarthritis study. Arthritis Rheum, 2009, 60(3):831-839.
18. Carthew RW, Sontheimer EJ. Origins and mechanisms of miRNAs and siRNAs. Cell, 2009, 136(4):642-655.
19. Zhang Z, Kang Y, Zhang Z, et al. Expression of microRNAs during chondrogenesis of human adipose-derived stem cells. Osteoarthritis Cartilage, 2012, 20(12):1638-1646.
20. Ukai T, Sato M, Akutsu H, et al. MicroRNA-199a-3p, microRNA-193b, and microRNA-320c are correlated to aging and regulate human cartilage metabolism. J Orthop Res, 2012, 30(12):1915-1922.
21. Swingler TE, Wheeler G, Carmont V, et al. The expression and function of microRNAs in chondrogenesis and osteoarthritis. Arthritis Rheum, 2012, 64(6):1909-1919.
22. BrophyRH, Rai MF, Zhang Z, et al. Molecular analysis of age and sex-related gene expression in meniscal tears with and without a concomitant anterior cruciate ligament tear. J Bone Joint Surg (Am), 2012, 94(5):385-393.
23. Henry S, Mascarenhas R, Kowalchuk D, et al. Medial meniscus tear morphology and chondral degeneration of the knee:is there a relationship? Arthroscopy, 2012, 28(8):1124-1134.e2.

Chinese Journal of Reparative and Reconstructive Surgery

EXPRESSIONS OF CARTILAGE DEGENERATIVE RELATED GENES AND microRNAs IN TORN MENISCUS

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