Chondrocyte-derived apoptotic bodies and calcification of articular cartilage

Abstract

Chondrocytes exposed to nitric oxide (NO) or antibody to Fas undergo cell death by apoptosis. This study examines structural and functional properties of chondrocyte-derived apoptotic bodies. In NO treated cartilage, the dense pericellular matrix that normally surrounds the cells is degraded and apoptotic bodies accumulate within and in the vicinity of the chondrocyte lacunae. Functional analysis shows that apoptotic bodies isolated from NO-treated chondrocytes or cartilage produce pyrophosphate. The levels of pyrophosphate produced by apoptotic bodies are increased by pretreatment of the chondrocytes with transforming growth factor ␤ and decreased by interleukin 1. Apoptotic bodies contain alkaline phosphatase and NTP pyrophosphohydrolase activities and can precipitate calcium. These results suggest that chondrocyte-derived apoptotic bodies express functional properties that may contribute to the pathologic cartilage calcification observed in aging and osteoarthritis.

Interleukin-1 Induces Pro-Mineralizing Activity of Cartilage Tissue Transglutaminase and Factor XIIIa

“…Moreover, despite the potential for direct expression of TGases to promote apoptosis in cultured cells, 20 -23,56,57 we did not observe significant induction of chondrocytic cell apoptosis, which promotes chondrocyte matrix calcification in vivo and in vitro in growth plate and articular chondrocytes. 4,58 Thus, the direct capacity of elevated Factor XIIIa and tTGase-associated TGase activities to promote chondrocytic cell matrix calcification in this study did not seem to be attributable to changes in PPi metabolism or apoptosis.…”

Increased apoptosis in human osteoarthritic cartilage corresponds to reduced cell density and expression of caspase‐3

“…Because age-related decreases in cartilage cellularity (19) are associated with an increased frequency of cartilage fibrillation (20), it would seem that reduced cellularity (due primarily to necrosis) is associated with cartilage fibrillation, but that apoptosis is not. However, it is worth noting that in other studies, investigators reported increasing numbers of apoptotic cells with increasing histologic grading (more fibrillation) of the OA cartilage (7,21).…”

Acetylated Low-Density Lipoprotein Stimulates Human Vascular Smooth Muscle Cell Calcification by Promoting Osteoblastic Differentiation and Inhibiting Phagocytosis

“…9,10 Similar structures derived from apoptotic VSMCs have been identified in human calcified arteries. 11 Like matrix vesicles, apoptotic bodies can accumulate calcium ions and calcify in vitro, 12,13 suggesting that they may be key sites for calcium crystal nucleation in plaques.…”