Open Access

Effect of chondrocyte mitochondrial dysfunction on cartilage degeneration: A possible pathway for osteoarthritis pathology at the subcellular level

  • Authors:
    • Heng Liu
    • Zhuoyang Li
    • Yongping Cao
    • Yunpeng Cui
    • Xin Yang
    • Zhichao Meng
    • Rui Wang
  • View Affiliations

  • Published online on: August 6, 2019     https://doi.org/10.3892/mmr.2019.10559
  • Pages: 3308-3316
  • Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Previous studies identified that chondrocyte apoptosis serves an important role in osteoarthritis (OA). However, the mechanisms of cartilage degeneration induced by apoptosis remain unclear. The present study investigated the role of mitochondrial dysfunction in OA pathology. A total of 30 cartilage samples presenting an Outerbridge score ranging between 0 and III were collected during total knee arthroplasty. Half of the samples were embedded for observation by transmission electron microscopy. The remaining samples were digested, and chondrocytes were isolated from normal and OA tissues. Subsequently, the enzymatic activity of factors of the mitochondrial respiratory chain (MRC), and mitochondrial membrane potential (Δψm), were quantified. Furthermore, chondrocytes were treated with rotenone (Ro), a specific inhibitor of the MRC, and curcumin (Cur), a mitochondrial protective agent, with the aim of analyzing the relationship between mitochondrial dysfunction and chondrocyte apoptosis. The mitochondria of OA chondrocytes showed apoptosis‑associated morphological alterations compared with normal cells. The Δψm and the activity of MRC enzymes were decreased in OA chondrocytes. Moreover, compared with normal chondrocytes, treatment with Ro was able to induce morphological changes reminiscent of the phenotype observed in OA chondrocytes. Additionally, Ro inhibited cellular proliferation, increased the apoptotic rate, and decreased the Δψm and the secretion of type II collagen. Furthermore, Cur could partly reverse the effects caused by treatment with Ro. The present data suggested that mitochondrial function was impaired in OA chondrocytes, resulting in an increased chondrocyte apoptosis and decreased type II collagen secretion. In addition, treatment with Cur protected the mitochondrial function and prevented cartilage degeneration. Collectively, the present results suggested that mitochondrial dysfunction may aggravate cartilage degeneration in the pathogenesis of OA.

References

1 

Blanco FJ, Guitian R, Vázquez-Martul E, de Toro FJ and Galdo F: Osteoarthritis chondrocytes die by apoptosis: A possible pathway for osteoarthritis pathology. Arthritis Rheum. 41:2841998. View Article : Google Scholar : PubMed/NCBI

2 

Buckwalter JA and Mankin HJ: Articular cartilage: Degeneration and osteoarthritis, repair, regeneration, and transplantation. Instr Course Lect. 47:487–504. 1998.PubMed/NCBI

3 

Otte P: Basic cell metabolism of articular cartilage. Manometric studies. Z Rheumatol. 50:304–312. 1991.PubMed/NCBI

4 

Falchuk KH, Goetzl EJ and Kulka JP: Respiratory gases of synovial fluids. An approach to synovial tissue circulatory-metabolic imbalance in rheumatoid arthritis. Am J Med. 49:223–231. 1970. View Article : Google Scholar : PubMed/NCBI

5 

Morgan-Hughes JA, Darveniza P, Kahn SN, Landon DN, Sherratt RM, Land JM and Clark JB: A mitochondrial myopathy characterized by a deficiency in reducible cytochrome b. Brain. 100:617–640. 1977. View Article : Google Scholar : PubMed/NCBI

6 

Beregi E and Regius O: Comparative morphological study of age related mitochondrial changes of the lymphocytes and skeletal muscle cells. Acta Morphol Hung. 35:219–224. 1987.PubMed/NCBI

7 

Takamiya S, Yanamura W, Capaldi RA, Kennaway NG, Bart R, Sengers RC, Trijbels JM and Ruitenbeek W: Mitochondrial myopathies involving the respiratory chain: A biochemical analysis. Ann N Y Acad Sci. 488:33–43. 1986. View Article : Google Scholar : PubMed/NCBI

8 

Ishikawa Y, Chin JE, Hubbard HL and Wuthier RE: Utilization and formation of amino acids by chicken epiphyseal chondrocytes: Comparative studies with cultured cells and native cartilage tissue. J Cell Physiol. 123:79–88. 1985. View Article : Google Scholar : PubMed/NCBI

9 

Kühn K, D'Lima DD, Hashimoto S and Lotz M: Cell death in cartilage. Osteoarthritis Cartilage. 12:1–16. 2004. View Article : Google Scholar : PubMed/NCBI

10 

Perkins G, Renken C, Martone ME, Young SJ, Ellisman M and Frey T: Electron tomography of neuronal mitochondria: Three-dimensional structure and organization of cristae and membrane contacts. J Struct Biol. 119:260–272. 1997. View Article : Google Scholar : PubMed/NCBI

11 

Maneiro E, Martín MA, de Andres MC, López-Armada MJ, Fernández-Sueiro JL, del Hoyo P, Galdo F, Arenas J and Blanco FJ: Mitochondrial respiratory activity is altered in osteoarthritic human articular chondrocytes. Arthritis Rheum. 48:700–708. 2003. View Article : Google Scholar : PubMed/NCBI

12 

Ernster L and Schatz G: Mitochondria: A historical review. J Cell Biol. 91:227s–255s. 1981. View Article : Google Scholar : PubMed/NCBI

13 

Chauvin C, De Oliveira F, Ronot X, Mousseau M, Leverve X and Fontaine E: Rotenone inhibits the mitochondrial permeability transition-induced cell death in U937 and KB cells. J Biol Chem. 276:41394–41398. 2001. View Article : Google Scholar : PubMed/NCBI

14 

Navarro A, Bández MJ, Gómez C, Repetto MG and Boveris A: Effects of rotenone and pyridaben on complex I electron transfer and on mitochondrial nitric oxide synthase functional activity. J Bioenerg Biomembr. 42:405–412. 2010. View Article : Google Scholar : PubMed/NCBI

15 

DiDonato S, Zeviani M, Giovannini P, Savarese N, Rimoldi M, Mariotti C, Girotti F and Caraceni T: Respiratory chain and mitochondrial DNA in muscle and brain in Parkinson's disease patients. Neurology. 43:2262–2268. 1993. View Article : Google Scholar : PubMed/NCBI

16 

Li N, Ragheb K, Lawler G, Sturgis J, Rajwa B, Melendez JA and Robinson JP: Mitochondrial complex I inhibitor rotenone induces apoptosis through enhancing mitochondrial reactive oxygen species production. J Biol Chem. 278:8516–8525. 2003. View Article : Google Scholar : PubMed/NCBI

17 

Jackson JK, Higo T, Hunter WL and Burt HM: The antioxidants curcumin and quercetin inhibit inflammatory processes associated with arthritis. Inflamm Res. 55:168–175. 2006. View Article : Google Scholar : PubMed/NCBI

18 

Cole GM, Teter B and Frautschy SA: Neuroprotective effects of curcumin. Adv Exp Med Biol. 595:197–212. 2007. View Article : Google Scholar : PubMed/NCBI

19 

Asai A and Miyazawa T: Dietary curcuminoids prevent high-fat diet-induced lipid accumulation in rat liver and epididymal adipose tissue. J Nutr. 131:2932–2935. 2001. View Article : Google Scholar : PubMed/NCBI

20 

Outerbridge RE: The etiology of chondromalacia patellae. J Bone Joint Surg Br. 43:752–757. 1961. View Article : Google Scholar : PubMed/NCBI

21 

Klagsbrun M: Large-scale preparation of chondrocytes. Methods Enzymol. 58:560–564. 1979. View Article : Google Scholar : PubMed/NCBI

22 

Morgan-Hughes JA, Hayes DJ, Clark JB, Landon DN, Swash M, Stark RJ and Rudge P: Mitochondrial encephalomyopathies: Biochemical studies in two cases revealing defects in the respiratory chain. Brain. 105:553–582. 1982. View Article : Google Scholar : PubMed/NCBI

23 

Shapiro HM: Membrane potential estimation by flow cytometry. Methods. 21:271–279. 2000. View Article : Google Scholar : PubMed/NCBI

24 

Kongtawelert P and Ghosh P: A new sandwich-ELISA method for the determination of keratan sulphate peptides in biological fluids employing a monoclonal antibody and labelled avidin biotin technique. Clin Chim Acta. 195:17–26. 1990. View Article : Google Scholar : PubMed/NCBI

25 

Aigner T, Kurz B, Fukui N and Sandell L: Roles of chondrocytes in the pathogenesis of osteoarthritis. Curr Opin Rheumatol. 14:578–584. 2002. View Article : Google Scholar : PubMed/NCBI

26 

Ma Q, Fang H, Shang W, Liu L, Xu Z, Ye T, Wang X, Zheng M, Chen Q and Cheng H: Superoxide flashes: Early mitochondrial signals for oxidative stress-induced apoptosis. J Biol Chem. 286:27573–27581. 2011. View Article : Google Scholar : PubMed/NCBI

27 

Higuchi M, Proske RJ and Yeh ET: Inhibition of mitochondrial respiratory chain complex I by TNF results in cytochrome c release, membrane permeability transition, and apoptosis. Oncogene. 17:2515–2524. 1998. View Article : Google Scholar : PubMed/NCBI

28 

Lee HC, Yin PH, Lu CY, Chi CW and Wei YH: Increase of mitochondria and mitochondrial DNA in response to oxidative stress in human cells. Biochem J. 348:425–432. 2000. View Article : Google Scholar : PubMed/NCBI

29 

Almeida A, Almeida J, Bolaños JP and Moncada S: Different responses of astrocytes and neurons to nitric oxide: The role of glycolytically generated ATP in astrocyte protection. Proc Natl Acad Sci USA. 98:15294–15299. 2001. View Article : Google Scholar : PubMed/NCBI

30 

Goossens V, Stangé G, Moens K, Pipeleers D and Grooten J: Regulation of tumor necrosis factor-induced, mitochondria- and reactive oxygen species-dependent cell death by the electron flux through the electron transport chain complex I. Antioxid Redox Signal. 1:285–295. 1999. View Article : Google Scholar : PubMed/NCBI

31 

Yook YH, Kang KH, Maeng O, Kim TR, Lee JO, Kang KI, Kim YS, Paik SG and Lee H: Nitric oxide induces BNIP3 expression that causes cell death in macrophages. Biochem Biophys Res Commun. 321:298–305. 2004. View Article : Google Scholar : PubMed/NCBI

32 

Distelmaier F, Koopman WJ, van den Heuvel LP, Rodenburg RJ, Mayatepek E, Willems PH and Smeitink JA: Mitochondrial complex I deficiency: From organelle dysfunction to clinical disease. Brain. 132:833–842. 2009. View Article : Google Scholar : PubMed/NCBI

33 

Reddy AC and Lokesh BR: Studies on spice principles as antioxidants in the inhibition of lipid peroxidation of rat liver microsomes. Mol Cell Biochem. 111:117–124. 1992.PubMed/NCBI

34 

Koiram PR, Veerapur VP, Kunwar A, Mishra B, Barik A, Priyadarsini IK and Mazhuvancherry UK: Effect of curcumin and curcumin copper complex (1:1) on radiation-induced changes of anti-oxidant enzymes levels in the livers of Swiss albino mice. J Radiat Res (Tokyo). 48:241–245. 2007. View Article : Google Scholar

35 

Le Goffe C, Vallette G, Jarry A, Bou-Hanna C and Laboisse CL: The in vitro manipulation of carbohydrate metabolism: A new strategy for deciphering the cellular defence mechanisms against nitric oxide attack. Biochem J. 3:643–648. 1999. View Article : Google Scholar

36 

Aulwurm UR and Brand KA: Increased formation of reactive oxygen species due to glucose depletion in primary cultures of rat thymocytes inhibits proliferation. Eur J Biochem. 267:5693–5698. 2000. View Article : Google Scholar : PubMed/NCBI

Related Articles

Journal Cover

October 2019
Volume 20 Issue 4

Print ISSN: 1791-2997
Online ISSN:1791-3004

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Liu, H., Li, Z., Cao, Y., Cui, Y., Yang, X., Meng, Z., & Wang, R. (2019). Effect of chondrocyte mitochondrial dysfunction on cartilage degeneration: A possible pathway for osteoarthritis pathology at the subcellular level. Molecular Medicine Reports, 20, 3308-3316. https://doi.org/10.3892/mmr.2019.10559
MLA
Liu, H., Li, Z., Cao, Y., Cui, Y., Yang, X., Meng, Z., Wang, R."Effect of chondrocyte mitochondrial dysfunction on cartilage degeneration: A possible pathway for osteoarthritis pathology at the subcellular level". Molecular Medicine Reports 20.4 (2019): 3308-3316.
Chicago
Liu, H., Li, Z., Cao, Y., Cui, Y., Yang, X., Meng, Z., Wang, R."Effect of chondrocyte mitochondrial dysfunction on cartilage degeneration: A possible pathway for osteoarthritis pathology at the subcellular level". Molecular Medicine Reports 20, no. 4 (2019): 3308-3316. https://doi.org/10.3892/mmr.2019.10559