Chondrocyte apoptosis

Loening AM, James IE, Levenston ME, Badger AM, Frank EH, Kurz B, Nuttall ME, Hung H-H, Blake SM, Grodzinsky AJ, Lark MW. Injurious mechanical compression of bovine articular cartilage indices chondrocyte apoptosis. Arch Biochem Biophys. 2000 381 205-212. 

Two further perspectives on the use of tetracychnes in rheumatoid arthritis have been pubhshed (14,15). In addition to an effect on matrix metalloproteinases, the authors focused on a potential antiarthritic action of tetracyclines by their effects in the interaction between the generation of nitric oxide, matrix metalloproteinase release, and chondrocyte apoptosis. Both minocychne and doxycycline inhibit the production of nitric oxide from human cartilage and murine macrophages (16) in concentrations that are achieved in vivo. The authors suggested that tetracyclines may have several potential chondroprotective effects direct inhibition of matrix metalloproteinase activity and, by inhibition of nitric oxide production, further reduction of matrix metalloproteinase activity, reversal of reduced matrix synthesis, and reduced chondrocyte apoptosis. 

Chondrocytes, the only cell type found in normal mature articular cartilage, are responsible for the maintenance and repair of this tissue, which happens to be the site of pathologic matrix remodeling and degradation in arthritis [51]. Indeed, chondrocyte apoptosis is a feature of osteoarthritic cartilage and is closely associated with extracellular matrix degradation. Fibrillated cartilage from osteoarthritic joints has been found to contain apoptotic cells in both the superficial and mid zones. In... 

Blanco, R J., Ochs, R. L., Schwarz, H., and Lotz, M. 1995. Chondrocyte apoptosis induced by nitric oxide. The American Journal of Pathology, 146, 75. 

McMahon Perhaps there is one natural example of that — the hypertrophic chondrocyte. The cells exit the cell cycle and then undergo growth, get bigger and bigger, and their eventual fate is apoptosis. One potential reason for this is that they have reached the limits of growth. 

Vu TH, Shipley JM, Bergers G, Berger JE, Helms JA, Hanahan D, et al. MMP-9/gelatinase B is a key regulator of growth plate angiogenesis and apoptosis of hypertrophic chondrocytes. Cell 1998 93 411-422. 

TGF-Pl, is the most abundant member of the TGF-P superfamily (Janssens et al, 2005). It impacts cell proliferation, differentiation, and apoptosis of both chondrocytes and osteoblasts (Selvamurugan et al, 2004). TGF-Pl signaling pathway occurs through Smad activation as well as through non-Smad pathways including activation of the ERK, JNK, and p38 MAPK pathways (Moustakas and Heldin, 2005, Blaney Davidson et al, 2007). TGF-P is found in the ECM surrounding osteoblasts as well as in chondrocytes. 

The effects of BMP-2 and BMP-7 on osteoblast differentiation, growth, proliferation, and apoptosis are well documented, and currently are used for clinical applications in the healing bone defects (Hay et al., 2004, Bessa et al., 2008). Of the BMP family, BMP-2, is known as a main factor in osteoblast homeostasis and BMP-7, is regarded as a main factor in chondrocyte function (Yoon and Fisher, 2007). 

TNF-a is a membrane-bound protein that once cleaved may act as a cytokine similar in function to IL-1 (Malemud, 2004). TNF-a is proteolytically cleaved by MMPs then binds with TNF-Rl or TNF-R2, both found on osteoblasts and chondrocytes (Malemud, 2004) Once bound the TNF receptor and ligand complex form a trimer and begins the signaling pathway. TNF receptors associate with tumor necrosis factor receptor-associated death domain protein (TRADD) to initiate the signaling pathways through FADD and TRAF2/5 (Yoon and Fisher, 2007, Nanes, 2003). TRAF 2/5 lead to the activation of the NF-kB and MAPK pathways (Yoon and Fisher, 2007, Malemud, 2004, Nanes, 2003). The FADD pathway initiates apoptosis through the activation of the caspase pathway. 

Wang, H., Wang, Z., Chen, J., and Wu, J. 2007. Apoptosis induced by NO via phosphorylation of p38 MAPK that stimulates NF-[kappa] B, p53 and caspase-3 activation in rabbit articular chondrocytes. Cell Biology International, 31,1027-1035. 

Wang, Y.-J., Shi, Q., Sun, P. et al. 2006. Insulin-Uke growth factor-1 treatment prevents anti-fas antibody-induced apoptosis in endplate chondrocytes. Spine, 31,736-74110.1097/01. brs.0000208128.49912.64. 

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