Abstract
Chondrocytes maintain the cartilaginous matrix and play an important role in endochondral ossification and cartilage repair. The regulation of chondrocyte proliferation and apoptosis is important in the pathology of cartilage and bone damage disorders. Recent studies have shown that glucocorticoids may induce apoptosis in chondrocytes. 11β-hydroxysteroid dehydrogenases (11β-HSDs) are microsomal enzymes that catalyze the interconversion of active 11-hydroxy-glucocorticoids and the inert 11-keto forms. We conducted an in vitro study to investigate the role of 11β-HSDs in apoptosis in femoral head chondrocytes. Our data showed that dexamethasone could induce chondrocyte apoptosis and cell viability reduction. Using Western blotting and real-time quantitative PCR, we observed that increased concentrations of dexamethasone increased the expression of 11β-HSD-1 and decreased the expression of 11β-HSD-2. Based on these results, we conclude that 11β-HSDs may be important for the regulation of glucocorticoid-induced apoptosis in chondrocytes. The present study demonstrates that glucocorticoids are able to induce both apoptosis in chondrocytes and a reduction in cell viability. Furthermore, 11β-HSDs may be important for the regulation of glucocorticoid-induced apoptosis in chondrocytes.
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References
Duan L, Liang Y, Ma B, Zhu W, Wang D (2015) Epigenetic regulation in chondrocyte phenotype maintenance for cell-based cartilage repair. Am J Transl Res 7:2127–2140
Hadoke PW, Kipari T, Seckl JR, Chapman KE (2013) Modulation of 11beta-hydroxysteroid dehydrogenase as a strategy to reduce vascular inflammation. Curr Atheroscler Rep 15:320
Hu J, Lu J, Lian G, Zhang J, Hecht JL, Sheen VL (2014) Filamin B regulates chondrocyte proliferation and differentiation through Cdk1 signaling. PLoS ONE 9:e89352
Hwang HS, Kim HA (2015) Chondrocyte Apoptosis in the Pathogenesis of Osteoarthritis. Int J Mol Sci 16:26035–26054
Kothapalli R, Aya-ay JP, Bian H, Garces A, Kim HK (2007) Ischaemic injury to femoral head induces apoptotic and oncotic cell death. Pathology 39:241–246
Lin Z, Willers C, Xu J, Zheng MH (2006) The chondrocyte: biology and clinical application. Tissue Eng 12:1971–1984
Ma R, Liu J, Wu L, Sun J, Yang Z, Yu C, Yuan P, Xiao X (2012) Differential expression of placental 11beta-hydroxysteroid dehydrogenases in pregnant women with diet-treated gestational diabetes mellitus. Steroids 77:798–805
Macova L, Sosvorova L, Vitku J, Bicikova M, Hill M, Zamrazilova H, Sedlackova B, Starka L (2015) Steroid hormones related to 11beta-hydroxysteroid dehydrogenase type 1 in treated obesity. Physiol Res 64(Suppl 2):S121–S133
Molitoris JK, McColl KS, Distelhorst CW (2011) Glucocorticoid-mediated repression of the oncogenic microRNA cluster miR-17 ~ 92 contributes to the induction of Bim and initiation of apoptosis. Mol Endocrinol 25:409–420
Moraes LA, Paul-Clark MJ, Rickman A, Flower RJ, Goulding NJ, Perretti M (2005) Ligand-specific glucocorticoid receptor activation in human platelets. Blood 106:4167–4175
O’Brien CA, Jia D, Plotkin LI, Bellido T, Powers CC, Stewart SA, Manolagas SC, Weinstein RS (2004) Glucocorticoids act directly on osteoblasts and osteocytes to induce their apoptosis and reduce bone formation and strength. Endocrinology 145:1835–1841
Shen C, Gu W, Cai GQ, Peng JP, Chen XD (2015a) Autophagy protects meniscal cells from glucocorticoids-induced apoptosis via inositol trisphosphate receptor signaling. Apoptosis 20:1176–1186
Shen C, Cai GQ, Peng JP, Chen XD (2015b) Autophagy protects chondrocytes from glucocorticoids-induced apoptosis via ROS/Akt/FOXO3 signaling. Osteoarthr Cartil 23:2279–2287
Smith LK, Shah RR, Cidlowski JA (2010) Glucocorticoids modulate microRNA expression and processing during lymphocyte apoptosis. J Biol Chem 285:36698–36708
Tu Y, Xue H, Xia Z, Cai M, Liu X, Ma T, Zhang C (2012) Effect of different concentrations of dexamethasone on apoptosis and expression of Fas/FasL in human osteoarthritis chondrocytes. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 26:536–541
Wang L, Luo DK, Pan ZY (2013) Expression of 11beta-HSD in steroid-induced avascular necrosis of the femoral head. Mol Med Rep 7:1482–1486
Xiao C, Srinivasan L, Calado DP, Patterson HC, Zhang B, Wang J, Henderson JM, Kutok JL, Rajewsky K (2008) Lymphoproliferative disease and autoimmunity in mice with increased miR-17-92 expression in lymphocytes. Nat Immunol 9:405–414
Xing W, Hao L, Yang X, Li F, Huo H (2014) Glucocorticoids induce apoptosis by inhibiting microRNA cluster miR1792 expression in chondrocytic cells. Mol Med Rep 10:881–886
Zhou PH, Liu SQ, Peng H (2008) The effect of hyaluronic acid on IL-1beta-induced chondrocyte apoptosis in a rat model of osteoarthritis. J Orthop Res 26:1643–1648
Zhou B, Chen D, Xu H, Zhang X (2017) Proliferation of rabbit chondrocyte and inhibition of IL-1beta-induced apoptosis through MEK/ERK signaling by statins. In Vitro Cell Dev Biol Anim 53:124–131
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The study was supported by the Hubei Province Natural Science Foundation of China.
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Bu, X., Zhou, F., Zhang, H. et al. Glucocorticoids Induces Apoptosis in Chondrocytes Through the Regulation of 11β-Hydroxysteroid Dehydrogenases (11β-HSDs). Int J Pept Res Ther 24, 519–524 (2018). https://doi.org/10.1007/s10989-017-9639-8
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DOI: https://doi.org/10.1007/s10989-017-9639-8