Chondrocyte apoptosis in endochondral ossification of chick sterna

Abstract

In the process of endochondral ossification, chondrocytes progress through a series of maturational changes, including division and hypertrophy, that culminate in chondrocyte loss and cartilage resorption. From an investigation of morphology, DNA fragmentation, and collagen synthesis in the developing chick sterna we have characterized chondrocytes death in this process. Light microscopy of resorbing sterna demonstrated chondrocyte condensation at the interface with the invading vasculature and electron microscopy demonstrated a range of chondrocyte morphologies, including retraction from the pericellular matrix, cytoplasmic and nuclear condensation, and vesiculation suggestive of sequential changes characteristic of apoptosis.Isolation and end-labeling of DNA from chick primary ossification centers demonstrated fragmentation to nucleosome sized units, only in primary ossification centers exhibiting active resorption, and in situ detection of DNA fragmentation showed a restriction to chondrocytes at the interface with invading blood. We conclude that terminal differentiation of chondrocytes results in death by an apoptotic process prior to resorption of the tissue and invasion by blood vessels. The extent of DNA fragmentation correlated closely with the proportion of cells displaying a condensed phenotype in contralateral primary ossification centers and peaked at an early stage of resorption, suggesting that chondrocyte apoptosis may be an initiating event in tissue resorption and vascular invasion. Comparison of DNA fragmentation with expression of the hypertrophic chondrocyte phenotype, as indicated by type X collagen synthesis, suggested that DNA fragmentation was a late event in the process of chondrocyte hypertrophy and probably corresponded with chondrocyte condensation. o 1995 Wiley-Liss, Inc.

The fate of soft callus chondrocytes during long bone fracture repair

“…Investigations into the removal of cells from the chondro-osseous J. L. Ford et id. I Journal .f Orthopuedic Reseurch 21 (2003) 54-61 5.5 junction in growth plate tissue have shown that terminal hypertrophic chondrocytes are removed from the epiphysis via apoptosis, which plays an important role in the ossification process [8,10,33]. Significantly higher levels of apoptosis have been observed in osteoarthritic cartilage compared to healthy cartilage [9,11,13,181 The precise mechanisms involved in chondrocyte loss from the soft callus have not been elucidated.…”

Aberrant death in dark chondrocytes of the avian growth plate

“…It is still a point of controversy whether all chondrocytes undergo apoptosis (Farnum and Wilson, 1990;Gibson et al, 1995;Hatori et al, 1995;Bronkers et al, 1996;Aizawa et al, 1997) or whether some survive to become bone-forming cells (Cancedda et al, 1995;Roach et al, 1995). Using morphological criteria, any chondrocyte with a condensed nucleus is often considered unviable or apoptotic.…”

Pivotal Role of Bcl-2 Family Proteins in the Regulation of Chondrocyte Apoptosis

“…In this process, chondrocytes first proliferate and then differentiate into mature hypertrophic chondrocytes, which mineralize the surrounding matrix that is finally replaced by bone (1). There is controversy as to the cell fate of hypertrophic chondrocytes, and several studies have shown that they undergo apoptosis after terminal differentiation (2)(3)(4). Apoptosis is a form of programmed cell death that is characterized by specific morphological and biochemical features, and is tightly regulated by extracellular stimuli and intracellular signaling pathways (5).…”