Subscribe to RSS
DOI: 10.3415/VCOT-07-06-0060
Dexamethasone induces apoptosis in proliferative canine tendon cells and chondrocytes
Publication History
Received: 08 June 2007
Accepted 21 February 2008
Publication Date:
19 December 2017 (online)
Summary
Dexamethasone (Dexa) has been commonly used in humans and domestic animals, particularly in the treatment of tendon injuries and cartilage degeneration. However, it is often associated with tendon rupture and impaired tendon and cartilage healing. In the present study, we investigated Dexa’s in vitro effects on the growth of cell proliferation and the induction of apoptosis in canine Achilles tendon cells and chondrocytes. Cell proliferation after treatment with Dexa for two to six days was quantified by a 2,3-bis{2-methoxy- 4-nitro-5-sulfophenyl}-2H-tetrazolium-5-carboxyanilide inner salt assay (XTT). The results showed that Dexa could inhibit the proliferation of tendon cells and chondrocytes at increasing concentrations (0.1–50 μg/ml) compared with untreated cells. Cell apoptosis was induced by Dexa, as evidenced by the typical nuclear apoptosis using Hoechst 33258 staining. Dexa increased the apoptosis of canine tendon cells and chondrocytes in a time-dependent manner. In canine tendon cells and chondrocytes that were treated with 25 and 50 μg/ml concentration of Dexa, the number of condensed apoptotic nuclei was significantly increased. In addition, culturing with Dexa and the glucocorticoid receptor blocker, mifepristone, significantly arrested apoptosis of tendon cells and chondrocytes. Based on our in vitro data, we hypothesized that in vivo treatment with glucocorticoids may diminish the proliferation of tendon and cartilage cells by increasing apoptosis and suppressing the proliferation. Our findings suggest that Dexa could be used with caution in dogs with articular or tendon problems.
-
References
- 1 Astrom M. Laser Doppler flowmetry in the assessment of tendon blood flow.. Scand J Med Sci Sports 2000; 10: 365-367.
- 2 O’Driscoll SW. The healing and regeneration of articular cartilage.. J Bone Joint Surg Am 1998; 80: 1795-1812.
- 3 Stewart MC, Saunders KM, Burton-Wurster N. et al. Phenotypic stability of articular chondrocytes in vitro: the effects of culture models, bone morphogenetic protein 2, and serum supplementation.. J Bone Miner Res 2000; 15: 166-174.
- 4 Nelson KH, Briner W, Jr Cummins J. Corticosteroid injection therapy for overuse injuries.. Am Fam Physicin 1995; 52: 1811-1816.
- 5 Hunziker EB. Biologic repair of articular cartilage. Defect models in experimental animals and matrix requirements.. Clin Orthop Relat Res 1999; 367: S135-146.
- 6 Smith AG, Kosygan K, Williams H. et al. Common extensor tendon rupture following corticosteroid injection for lateral tendinosis of the elbow.. Br J Sports Med 1999; 33: 423-425.
- 7 Kotnis RA, Halstead JC, Hormbrey PJ. Atraumatic bilateral Achilles tendon rupture: an association of systemic steroid treatment.. J Accid Emerg Med 1999; 16: 378-379.
- 8 Wong MW, Tang YY, Lee SK. et al. Effect of dexamethasone on cultured human tenocytes and its reversibility by platelet-derived growth factor.. J Bone Joint Surg Am 2003; 85: 1914-1920.
- 9 Fredberg U. Local corticosteroid injection in Sport: review of literature and guideslines for treatment.. Scand J Med Sci Sports 1997; 7: 131-139.
- 10 Hayes DW, Jr Gilbertson EK, Mandracchia VJ. et al. Tendon pathology in the foot. The use of corticosteroid injection therapy.. Clin Podiatr Med Surg 2000; 17: 723-735.
- 11 Kapetanos G. The effect of the local corticosteroids on the healing and biomechanical properties of the partially injured tendon.. Clin Orthop Relat Res 1982; 163: 170-179.
- 12 Tatari H, Kosay C, Baran O. et al. Deleterious effects of local corticosteroid injections on the Achilles tendon of rats.. Arch Orthop Trauma Surg 2001; 121: 333-337.
- 13 Chrysis D, Zaman F, Chagin AS. et al. Dexamethasone induces apoptosis in proliferative chondrocytes through activation of caspases and suppression of the Akt-phosphatidylinositol 3’-kinase signaling pathway.. Endocrinology 2005; 146: 1391-1397.
- 14 Kruman II, Matylevich NP, Beletsky IP. et al. Apoptosis of murine BW 5147 thymoma cells induced by dexamethasone and gamma-irradiation.. J Cell Physiol 1991; 148: 267-273.
- 15 Ranta F, Avram D, Berchtold S. et al. Dexamethasone induces cell death in insulin-secreting cells, an effect reversed by exendin-4.. Diabetes 2006; 55: 1380-1390.
- 16 Webster JC, Huber RM, Hanson RL. et al. Dexamethasone and tumor necrosis factor-alpha act together to induce the cellular inhibitor of apoptosis-2 gene and prevent apoptosis in a variety of cell types.. Endocrinology. 2002; 143 (03) 866-874.
- 17 Brittberg M, Lindahl A, Nilsson A. et al. Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation.. JN Engl Med 1994; 331: 889-895.
- 18 Wiggins ME, Fadale PD, Ehrlich MG. et al. Effects of local injection of corticosteroids on the healing of ligaments. A follow-up report.. J Bone Joint Surg Am 1995; 77: 1682-1691.
- 19 Scutt A, Bertram P, Bräutigam M.. The role of glucocorticoids and prostaglandin E2 in the recruitment of bone marrow mesenchymal cells to the osteoblastic lineage: positive and negative effects.. Calcif Tissue Int 1996; 59: 154-162.
- 20 Wong MW, Tang YN, Fu SC. et al. Triamcinolone suppressed human tenocyte cellular activity and collagen synthesis.. Clin Orthop Relat Res 2004; 421: 277-281.
- 21 Wong MW, Tang YY, Lee SK. et al. Glucocortocoids suppressed proteoglycan production by human tenocytes.. Acta Orthop 2005; 76: 927-931.
- 22 Scutt N, Rolf CG, Scutt A. Glucocorticoids inhibit tenocyte proliferation and tendon progenitor cell recruitment.. J Orthop Res 2006; 24: 173-182.
- 23 Yuan J, Murrell GA, Trickett A. et al. Involment of cytochrome C release and caspase-3 activation in the oxidative stress-induced apoptosis in human tendon fibroblasts.. Biochem Biophys Acta 2003; 1641: 35-41.
- 24 Malark JA, Nixon AJ, Skinner KL. et al. Characteristics of digital flexor tendon sheath fluid from clinically normal horses.. Am J Vet Res 1991; 52: 1292-1294.
- 25 Hagberg L, Heinegard D, Ohlsson K. The contents of macromolecule solutes in flexor tendon sheath fluid and their relation to synovial fluid.. A quantitative analysis. J. Hand Surg [Br] 1992; 17: 167-171.
- 26 Kannus P, Jozsa L. Histopathological changes proceding spontaneous rupture of tendon. A controlled study of 891 patients.. J Bone Joint Surg Am 1991; 73: 1507-1525.
- 27 Barnes PJ. Anti-inflammatory actions of glucocorticoids: molecular mechanisms.. Clin Sci (Lond) 1998; 94: 557-572.
- 28 Fukuzuka K, Edwards CK, III Clare-Salzler M. et al. Glucocortiocoid-induced, caspase-dependent organ apoptosis early after burn injury.. Am J Physiol Regul Integr Comp Physiol 2000; 278: 1005-1018.
- 29 Loew D, Schuster O, Graul EH. Dose-dependent pharmacokinetics of dexamethasone.. Eur J Clin Pharmacol 1986; 30: 225-230.