An ultrastructural study of chondroptosis: programmed cell death in degenerative intervertebral discs in vivo

Abstract

Apoptosis has been regarded to mediate intervertebral disc degeneration (IDD); however, the basic question of how the apoptotic bodies are cleared in the avascular intervertebral disc without phagocytes, which are essential to apoptosis, remains to be elucidated. Our goals were to investigate the ultrastructure of nucleus pulposus (NP) cells undergoing chondroptosis, a variant of apoptotic cell death, in a rabbit annular needle-puncture model of IDD. Experimental IDD was induced by puncturing discs with a 16-G needle in New Zealand rabbits. At 4 and 12 weeks after puncture, progressive degeneration was demonstrated by X-ray, magnetic resonance imaging and histological staining. TUNEL staining suggested a significant increase in the apoptosis index in the degenerated NP. However, the percentage of apoptotic cells with the classic ultrastructure morphology was much less than that with chondroptotic ultrastructure morphology under transmission electron microscopy (TEM). The chondroptotic cells from the early to late stage were visualized under TEM. In addition, the percentage of chondroptotic cells was significantly enhanced in the degenerated NP. Furthermore, 'paralyzed' cells were found in the herniated tissue. Western blotting revealed an increase in caspase3 expression in the degenerated NP. The expression of the Golgi protein (58K) was increased by the fourth week after puncture but decreased later. These findings indicate that chondroptosis is a major type of programmed cell death in the degenerated rabbit NP that may be related to the progressive development of IDD.

Intervertebral disc cell chondroptosis elicits neutrophil response inStaphylococcus aureusspondylodiscitis

“…However, since Annexin V staining is just an indicator for any type of regulated cell death, it is crucial to further determine the involved regulated cell death pathways (37). Since chondroptosis is regarded as the de facto regulated IVD cell death (20,23), it is not surprising that IVD cells underwent chondroptosis upon S. aureus challenge, as corroborated by TEM, especially since it was previously observed that IVD cells underwent caspase-mediated regulated cell death upon C. acnes challenge (18). One can assume that chondroptosis might be a conserved response of IVD cells towards bacterial encounter.…”

“…Regulated IVD cell death has been extensively studied in connection to its potential role in IVD degeneration. Studies showed that in sterile IVD inflammation, IVD cells frequently undergo regulated cell death morphologically similar to chondroptosis (19,20). Chondroptosis was first described for articular chondrocytes in the growth plate of rabbit femurs (21,22) and considered to be an apoptotic-derived regulated cell death type, characterized by the activation of apoptotic caspases and formation of autophagic vacuoles to sequester and degrade cellular material (23).…”

Neonatal enthesis healing involves non-inflammatory formation of acellular scar through ECM secretion by resident cells

“…The copyright holder for this preprint this version posted December 20, 2021. ; https://doi.org/10.1101/2021.12.20.473454 doi: bioRxiv preprint apparatus and endoplasmic reticulum (ER), autophagic vacuoles, patchy condensations of nuclei and blebbing of cytoplasmic material and activation of apoptosis via caspase-3 and caspase-9 involvement [17][18][19][20][21][22] . In full-thickness injuries, the damage is deeper and reaches into the subchondral bone, thereby creating a pathway into the vascular bone marrow 23 .…”

“…Partial-thickness injuries do not heal spontaneously, as inflammation and blood vessels are absent 16 . Following injury, cells within the wound margins undergo chondroptosis, a variant of cell death that is characterized by an increase in Golgi apparatus and endoplasmic reticulum (ER), autophagic vacuoles, patchy condensations of nuclei and blebbing of cytoplasmic material and activation of apoptosis via caspase-3 and caspase-9 involvement 17–22 . In full-thickness injuries, the damage is deeper and reaches into the subchondral bone, thereby creating a pathway into the vascular bone marrow 23 .…”

Icariin Attenuates Serum Deprived-Induced Premature Senescence in Rat Annulus Fibrosus Cells and Ameliorates Disc Degeneration In Vivo

“…Research showed annulus fibrosus is different in young and old sample using intralamellar matrix of single lamellae [4], Quantitative proteomic analysis [5] and medical imaging methods [6]. Although death and reduction of extracelluar matrix in nucleus pulposus cells contribute to the degeneration of intervertebral disc [7], the senescence and fracture of annulus fibrosus is cannot be neglected.…”