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Ann Rheum Dis. 2000 Dec; 59(12): 959–965.
PMCID: PMC1753049

Apoptosis in normal and osteoarthritic human articular cartilage


OBJECTIVES—To investigate whether apoptosis occurs in osteoarthritis (OA), and if this phenomenon is modulated by human recombinant interleukin 1β (hrIL1β).
METHODS—Human articular cartilage samples were obtained at the time of hip arthroplasty because of femoral neck fracture (normal cartilage) (n=4) or advanced coxarthrosis (OA cartilage) (n=14). Apoptotic chondrocytes, isolated by collagenase digestion and cultivated for 24 hours, or present in situ in frozen cartilage sections, were quantified by fluorescent microscopy using two apoptosis markers: the TUNEL reaction, which detects nuclear DNA fragmentation, and Annexin-V-fluos, which labels at the membrane level the externalisation of phosphatidylserine.
RESULTS—In OA cartilage 18-21% of chondrocytes showed apoptotic features, compared with 2-5% in normal cartilage. The results were similar for the two comparative studies (in situ and in vitro) and for both apoptosis markers. Moreover, hrIL1β increased the apoptosis rate in vitro in a dose dependent manner in OA and normal chondrocytes.
CONCLUSION—These results suggest that apoptosis may be an important factor in the evolution of OA and may be a new target for treatment of OA.

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Selected References

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  • Hamerman D. Clinical implications of osteoarthritis and ageing. Ann Rheum Dis. 1995 Feb;54(2):82–85. [PMC free article] [PubMed]
  • Vignon E, Arlot M, Meunier P, Vignon G. Quantitative histological changes in osteoarthritic hip cartilage. Morphometric analysis of 29 osteoarthritic and 26 normal human femoral heads. Clin Orthop Relat Res. 1974;(103):269–278. [PubMed]
  • Vignon E, Arlot M, Patricot LM, Vignon G. The cell density of human femoral head cartilage. Clin Orthop Relat Res. 1976 Nov-Dec;(121):303–308. [PubMed]
  • Harmand MF, Duphil R, Blanquet P. Proteoglycan synthesis in chondrocyte cultures from osteoarthrotic and normal human articular cartilage. Biochim Biophys Acta. 1982 Aug 6;717(2):190–202. [PubMed]
  • Nakajima T, Aono H, Hasunuma T, Yamamoto K, Shirai T, Hirohata K, Nishioka K. Apoptosis and functional Fas antigen in rheumatoid arthritis synoviocytes. Arthritis Rheum. 1995 Apr;38(4):485–491. [PubMed]
  • Matsumoto S, Müller-Ladner U, Gay RE, Nishioka K, Gay S. Ultrastructural demonstration of apoptosis, Fas and Bcl-2 expression of rheumatoid synovial fibroblasts. J Rheumatol. 1996 Aug;23(8):1345–1352. [PubMed]
  • Firestein GS, Yeo M, Zvaifler NJ. Apoptosis in rheumatoid arthritis synovium. J Clin Invest. 1995 Sep;96(3):1631–1638. [PMC free article] [PubMed]
  • Hoa TT, Hasunuma T, Aono H, Masuko K, Kobata T, Yamamoto K, Sumida T, Nishioka K. Novel mechanisms of selective apoptosis in synovial T cells of patients with rheumatoid arthritis. J Rheumatol. 1996 Aug;23(8):1332–1337. [PubMed]
  • Blanco FJ, Guitian R, Vázquez-Martul E, de Toro FJ, Galdo F. Osteoarthritis chondrocytes die by apoptosis. A possible pathway for osteoarthritis pathology. Arthritis Rheum. 1998 Feb;41(2):284–289. [PubMed]
  • Hashimoto S, Takahashi K, Amiel D, Coutts RD, Lotz M. Chondrocyte apoptosis and nitric oxide production during experimentally induced osteoarthritis. Arthritis Rheum. 1998 Jul;41(7):1266–1274. [PubMed]
  • Hashimoto S, Ochs RL, Komiya S, Lotz M. Linkage of chondrocyte apoptosis and cartilage degradation in human osteoarthritis. Arthritis Rheum. 1998 Sep;41(9):1632–1638. [PubMed]
  • Kerr JF, Wyllie AH, Currie AR. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer. 1972 Aug;26(4):239–257. [PMC free article] [PubMed]
  • Majno G, Joris I. Apoptosis, oncosis, and necrosis. An overview of cell death. Am J Pathol. 1995 Jan;146(1):3–15. [PMC free article] [PubMed]
  • Bosman FT, Visser BC, van Oeveren J. Apoptosis: pathophysiology of programmed cell death. Pathol Res Pract. 1996 Jul;192(7):676–683. [PubMed]
  • Adams CS, Horton WE., Jr Chondrocyte apoptosis increases with age in the articular cartilage of adult animals. Anat Rec. 1998 Apr;250(4):418–425. [PubMed]
  • Palmer RM, Hickery MS, Charles IG, Moncada S, Bayliss MT. Induction of nitric oxide synthase in human chondrocytes. Biochem Biophys Res Commun. 1993 May 28;193(1):398–405. [PubMed]
  • Maier R, Bilbe G, Rediske J, Lotz M. Inducible nitric oxide synthase from human articular chondrocytes: cDNA cloning and analysis of mRNA expression. Biochim Biophys Acta. 1994 Sep 21;1208(1):145–150. [PubMed]
  • Evans CH. Nitric oxide: what role does it play in inflammation and tissue destruction? Agents Actions Suppl. 1995;47:107–116. [PubMed]
  • Taskiran D, Stefanovic-Racic M, Georgescu H, Evans C. Nitric oxide mediates suppression of cartilage proteoglycan synthesis by interleukin-1. Biochem Biophys Res Commun. 1994 Apr 15;200(1):142–148. [PubMed]
  • Blanco FJ, Ochs RL, Schwarz H, Lotz M. Chondrocyte apoptosis induced by nitric oxide. Am J Pathol. 1995 Jan;146(1):75–85. [PMC free article] [PubMed]
  • Hayashi T, Abe E, Yamate T, Taguchi Y, Jasin HE. Nitric oxide production by superficial and deep articular chondrocytes. Arthritis Rheum. 1997 Feb;40(2):261–269. [PubMed]
  • Grabowski PS, Macpherson H, Ralston SH. Nitric oxide production in cells derived from the human joint. Br J Rheumatol. 1996 Mar;35(3):207–212. [PubMed]
  • Altman R, Alarcón G, Appelrouth D, Bloch D, Borenstein D, Brandt K, Brown C, Cooke TD, Daniel W, Feldman D, et al. The American College of Rheumatology criteria for the classification and reporting of osteoarthritis of the hip. Arthritis Rheum. 1991 May;34(5):505–514. [PubMed]
  • Gavrieli Y, Sherman Y, Ben-Sasson SA. Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation. J Cell Biol. 1992 Nov;119(3):493–501. [PMC free article] [PubMed]
  • Martin SJ, Reutelingsperger CP, McGahon AJ, Rader JA, van Schie RC, LaFace DM, Green DR. Early redistribution of plasma membrane phosphatidylserine is a general feature of apoptosis regardless of the initiating stimulus: inhibition by overexpression of Bcl-2 and Abl. J Exp Med. 1995 Nov 1;182(5):1545–1556. [PMC free article] [PubMed]
  • Mollenhauer J, Mok MT, King KB, Gupta M, Chubinskaya S, Koepp H, Cole AA. Expression of anchorin CII (cartilage annexin V) in human young, normal adult, and osteoarthritic cartilage. J Histochem Cytochem. 1999 Feb;47(2):209–220. [PubMed]
  • Aizawa T, Kokubun S, Tanaka Y. Apoptosis and proliferation of growth plate chondrocytes in rabbits. J Bone Joint Surg Br. 1997 May;79(3):483–486. [PubMed]
  • Hashimoto S, Setareh M, Ochs RL, Lotz M. Fas/Fas ligand expression and induction of apoptosis in chondrocytes. Arthritis Rheum. 1997 Oct;40(10):1749–1755. [PubMed]
  • Martel-Pelletier J, McCollum R, DiBattista J, Faure MP, Chin JA, Fournier S, Sarfati M, Pelletier JP. The interleukin-1 receptor in normal and osteoarthritic human articular chondrocytes. Identification as the type I receptor and analysis of binding kinetics and biologic function. Arthritis Rheum. 1992 May;35(5):530–540. [PubMed]
  • Gibson G, Lin DL, Roque M. Apoptosis of terminally differentiated chondrocytes in culture. Exp Cell Res. 1997 Jun 15;233(2):372–382. [PubMed]
  • Lotz M, Hashimoto S, Kühn K. Mechanisms of chondrocyte apoptosis. Osteoarthritis Cartilage. 1999 Jul;7(4):389–391. [PubMed]
  • Cooper C, Inskip H, Croft P, Campbell L, Smith G, McLaren M, Coggon D. Individual risk factors for hip osteoarthritis: obesity, hip injury, and physical activity. Am J Epidemiol. 1998 Mar 15;147(6):516–522. [PubMed]
  • Oliveria SA, Felson DT, Cirillo PA, Reed JI, Walker AM. Body weight, body mass index, and incident symptomatic osteoarthritis of the hand, hip, and knee. Epidemiology. 1999 Mar;10(2):161–166. [PubMed]
  • Vingård E. Overweight predisposes to coxarthrosis. Body-mass index studied in 239 males with hip arthroplasty. Acta Orthop Scand. 1991 Apr;62(2):106–109. [PubMed]
  • Felson DT, Zhang Y. An update on the epidemiology of knee and hip osteoarthritis with a view to prevention. Arthritis Rheum. 1998 Aug;41(8):1343–1355. [PubMed]

Figures and Tables

Figure 1
Detection of apoptosis by immunofluorescence on isolated OA chondrocytes by collagenase digestion (A and C) and in situ on fresh frozen OA cartilage (B and D). (A and B) Chondrocytes were fixed, permeabilised, and processed by the TUNEL reaction mixture. ...
Figure 2
Comparative study of normal and OA chondrocytes using the TUNEL reaction and Annexin-V labelling in chondrocytes isolated by collagenase digestion. The ratio of apoptotic cells/total cells was calculated as a percentage. Values are means (SEM) from four ...
Figure 3
Comparative study of normal and OA cartilage using the TUNEL reaction and Annexin-V labelling on frozen cartilage sections. The ratio of apoptotic cells/total cells was calculated as a percentage. Data are representative results from four experiments ...
Figure 4
Induction of apoptosis in OA chondrocytes by human recombinant interleukin 1β (hrIL1β). (A) Untreated control OA human chondrocytes. (B) OA human articular chondrocytes in primary culture stimulated with 10 ng/ml of hrIL1β ...
Figure 5
Percentage of apoptotic chondrocytes as a function of aging in the patients with OA and normal patients. Cells were isolated by collagenase digestion, and apoptosis in these isolated cells was analysed by TUNEL reaction labelling. Values are means (SEM) ...

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