title: Insights on Molecular Mechanisms of Chondrocytes Death in Osteoarthritis.
abstract: Osteoarthritis (OA) is a joint pathology characterized by progressive cartilage degradation. Medical care is mainly based on alleviating pain symptoms. Compelling studies report the presence of empty lacunae and hypocellularity in cartilage with aging and OA progression, suggesting that chondrocyte cell death occurs and participates to OA development. However, the relative contribution of apoptosis per se in OA pathogenesis appears complex to evaluate. Indeed, depending on technical approaches, OA stages, cartilage layers, animal models, as well as in vivo or in vitro experiments, the percentage of apoptosis and cell death types can vary. Apoptosis, chondroptosis, necrosis, and autophagic cell death are described in this review. The question of cell death causality in OA progression is also addressed, as well as the molecular pathways leading to cell death in response to the following inducers: Fas, Interleukin-1β (IL-1β), Tumor Necrosis factor-α (TNF-α), leptin, nitric oxide (NO) donors, and mechanical stresses. Furthermore, the protective role of autophagy in chondrocytes is highlighted, as well as its decline during OA progression, enhancing chondrocyte cell death; the transition being mainly controlled by HIF-1α/HIF-2α imbalance. Finally, we have considered whether interfering in chondrocyte apoptosis or promoting autophagy could constitute therapeutic strategies to impede OA progression.
authors.affiliation: Laboratory of Rheumatology, Groupe Interdisciplinaire de Génoprotéomique Appliquée (GIGA) Research, Centre Hospitalier Universitaire (CHU) de Liège, University of Liège, 4000 Liège, Belgium. edith.charlier@chu.ulg.ac.be.
authors.forename: Edith
authors.initials: E
authors.lastname: Charlier
authors.affiliation: Laboratory of Rheumatology, Groupe Interdisciplinaire de Génoprotéomique Appliquée (GIGA) Research, Centre Hospitalier Universitaire (CHU) de Liège, University of Liège, 4000 Liège, Belgium. biserka.relic@chu.ulg.ac.be.
authors.forename: Biserka
authors.initials: B
authors.lastname: Relic
authors.affiliation: Laboratory of Rheumatology, Groupe Interdisciplinaire de Génoprotéomique Appliquée (GIGA) Research, Centre Hospitalier Universitaire (CHU) de Liège, University of Liège, 4000 Liège, Belgium. celine.deroyer@ulg.ac.be.
authors.forename: Céline
authors.initials: C
authors.lastname: Deroyer
authors.affiliation: Laboratory of Rheumatology, Groupe Interdisciplinaire de Génoprotéomique Appliquée (GIGA) Research, Centre Hospitalier Universitaire (CHU) de Liège, University of Liège, 4000 Liège, Belgium. olivier.malaise@chu.ulg.ac.be.
authors.forename: Olivier
authors.initials: O
authors.lastname: Malaise
authors.affiliation: Laboratory of Rheumatology, Groupe Interdisciplinaire de Génoprotéomique Appliquée (GIGA) Research, Centre Hospitalier Universitaire (CHU) de Liège, University of Liège, 4000 Liège, Belgium. sophie.neuville@chu.ulg.ac.be.
authors.forename: Sophie
authors.initials: S
authors.lastname: Neuville
authors.affiliation: Laboratory of Rheumatology, Groupe Interdisciplinaire de Génoprotéomique Appliquée (GIGA) Research, Centre Hospitalier Universitaire (CHU) de Liège, University of Liège, 4000 Liège, Belgium. julie.collee@student.ulg.ac.be.
authors.forename: Julie
authors.initials: J
authors.lastname: Collée
authors.affiliation: Laboratory of Rheumatology, Groupe Interdisciplinaire de Génoprotéomique Appliquée (GIGA) Research, Centre Hospitalier Universitaire (CHU) de Liège, University of Liège, 4000 Liège, Belgium. michel.malaise@ulg.ac.be.
authors.forename: Michel G
authors.initials: MG
authors.lastname: Malaise
authors.affiliation: Laboratory of Rheumatology, Groupe Interdisciplinaire de Génoprotéomique Appliquée (GIGA) Research, Centre Hospitalier Universitaire (CHU) de Liège, University of Liège, 4000 Liège, Belgium. ddeseny@chu.ulg.ac.be.
authors.forename: Dominique
authors.initials: D
authors.lastname: De Seny
mesh_terms: D000375:Aging; D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy / Q000502:physiology*; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D002358:Cartilage, Articular / Q000473:pathology*; D019902:Chondrocytes / Q000378:metabolism*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D020738:Leptin / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D010003:Osteoarthritis / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D051017:Apoptosis Regulatory Proteins; D051792:Basic Helix-Loop-Helix Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D053583:Interleukin-1beta; D020738:Leptin; D009569:Nitric Oxide; D014409:Tumor Necrosis Factor-alpha; D000099162:Endothelial PAS Domain-Containing Protein 1; C421307:FAIM protein, human; C497442:HIF1A protein, human; C508585:IL1B protein, human
keywords: apoptosis; autophagy; chondrocytes; chondroptosis; necrosis; osteoarthritis