Chondrocyte death involvement in osteoarthritis

Abstract

Chondrocyte apoptosis is known to contribute to articular cartilage damage in osteoarthritis and is correlated to a number of cartilage disorders. Micromass cultures represent a convenient means for studying chondrocyte biology, and, in particular, their death. In this review, we focused the different kinds of chondrocyte death through a comparison between data reported in the literature. Chondrocytes show necrotic features and, occasionally, also apoptotic features, but usually undergo a new form of cell death called Chondroptosis, which occurs in a non-classical manner. Chondroptosis has some features in common with classical apoptosis, such as cell shrinkage, chromatin condensation, and involvement, not always, of caspases. The most crucial peculiarity of chondroptosis relates to the ultimate elimination of cellular remnants. Independent of phagocytosis, chondroptosis may serve to eliminate cells without inflammation in situations in which phagocytosis would be difficult. This particular death mechanism is probably due to the unusual condition chondrocytes both in vivo and in micromass culture. This review highlights on the morpho-fuctional alterations of articular cartilage and focus attention on various types of chondrocyte death involved in this degeneration. The death features have been detailed and discussed through in vitro studies based on tridimensional chondrocyte culture (micromasses culture). The study of this particular mechanism of cartilage death and the characterization of different biological and biochemical underlying mechanisms can lead to the identification of new potentially therapeutic targets in various joint diseases.

Keywords: Apoptosis; Chondrocyte; Micromass; Necrosis; Osteoarthritis.

Fig. 1

A Normal cartilage section is displayed after toluidine blu staining; this is a cartilage of young patient. B Schematic representation of articular cartilage. C, D, E, F TEM of osteoarthritis cartilage; image of small fragment of cartilage derived from old patient with articular cartilage degeneration

Fig. 2

Optical microscope (A) and TEM of control chondrocyte in micromass (B–I). Micromass appears as a sphere of 1 mm diameter (A). Flattened chondrocyte at micromass periphery and ovoidalin in the inner micromass (B) can be observed. Occasionally, they are scattered in cartilage cavities, also called lacunae (A, D) (*). The progressive ECM assembling appears mainly distributed in close cell proximity (E). Chondrocyte are surrounded by a complex matrix, formed by proteoglycans (E, →) and collagen fibres (F, ►). Diffuse nuclear chromatin (B, C, F, G, H, I) and well preserved organelle (G, H, I) can be observed. A Bar 10 µm; B, C, E, F, G, H, I, Bar 2 µm; D Bar 5 µm

Fig. 3

TEM of chondrocyte necrosis. The plasma membrane integrity is not maintained in necrotic chondrocytes (A, B). Cytoplasm appears emptied and total cell lysis can be observed (A, B). A, B Bar 2

Fig. 4

TEM of chondrocyte apoptosis. Nucleus appears lobed (A) and presents condensed chromatin, localized at the nuclear periphery (A, B). The outer nuclear membrane appears occasionally detached at condensed chromatin level (C). Some nuclear pores appear close to diffuse chromatin (C, D). Rounding and swollen mitochondria can be revealed (A, C) (m). True apoptotic bodies are only rarely found (E). A, C, D Bar 1 µm. B Bar 2 µm

Fig. 5

TEM of chondrocyte chondroptosis. Cellular shrinkage and chromatin condensation (A, B) can be observed. Chromatin is marginated into small patches spread throughout the nucleus (A, B). The presence of autophagic vacuoles (C) and rough endoplasmic reticulum (RER) appear increased (D). Nucleus, with very condensed chromatin, displays electron-dense agglomerates in close proximity of nuclear membrane (D, E)

Fig. 6

TUNEL reaction (A, B, C, D) and caspase activation (E). Control cells appear negatively stained (A) but after staurosporine (B), UVB (C), and hyperthermia (D) treatment positive cells can be observed. E Caspase-8, -9, -3, and -6 expression in control, staurosporine (ST), hyperthermia (HT), and UVB (UV) conditions. A, B, C, D, E, F Bar 1 µm

Fig. 7

Illustration of the main and crucial differences between classical apoptosis and chondroptosis