title: Aging-related loss of the chromatin protein HMGB2 in articular cartilage is linked to reduced cellularity and osteoarthritis.
abstract: Osteoarthritis (OA) is the most common joint disease and typically begins with an aging-related disruption of the articular cartilage surface. Mechanisms leading to the aging-related cartilage surface degeneration remain to be determined. Here, we demonstrate that nonhistone chromatin protein high-mobility group box (HMGB) protein 2 is uniquely expressed in the superficial zone (SZ) of human articular cartilage. In human and murine cartilage, there is an aging-related loss of HMGB2 expression, ultimately leading to its complete absence. Mice genetically deficient in HMGB2 (Hmgb2(-/-)) show earlier onset of and more severe OA. This is associated with a profound reduction in cartilage cellularity attributable to increased cell death. These cellular changes precede glycosaminoglycan depletion and progressive cartilage erosions. Chondrocytes from Hmgb2(-/-) mice are more susceptible to apoptosis induction in vitro. In conclusion, HMGB2 is a transcriptional regulator specifically expressed in the SZ of human articular cartilage and supports chondrocyte survival. Aging is associated with a loss of HMGB2 expression and reduced cellularity, and this contributes to the development of OA.
authors.affiliation: Division of Arthritis Research, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Noboru
authors.initials: N
authors.lastname: Taniguchi
authors.forename: Beatriz
authors.initials: B
authors.lastname: Caramés
authors.forename: Lorenza
authors.initials: L
authors.lastname: Ronfani
authors.forename: Ulrich
authors.initials: U
authors.lastname: Ulmer
authors.forename: Setsuro
authors.initials: S
authors.lastname: Komiya
authors.forename: Marco E
authors.initials: ME
authors.lastname: Bianchi
authors.forename: Martin
authors.initials: M
authors.lastname: Lotz
mesh_terms: D000375:Aging / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D017209:Apoptosis; D002358:Cartilage, Articular / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D002470:Cell Survival; D002843:Chromatin / Q000378:metabolism*; D005786:Gene Expression Regulation; D024261:HMGB2 Protein / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007596:Joints / Q000201:enzymology / Q000473:pathology; D020782:Matrix Metalloproteinases / Q000378:metabolism; D051379:Mice; D010003:Osteoarthritis / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D021381:Protein Transport; D011509:Proteoglycans / Q000378:metabolism; D000099158:Proteoglycan 4
chemical_list: D002843:Chromatin; D024261:HMGB2 Protein; D020782:Matrix Metalloproteinases; D011509:Proteoglycans; C498837:Prg4 protein, mouse; D000099158:Proteoglycan 4