Aging-related loss of the chromatin protein HMGB2 in articular cartilage is linked to reduced cellularity and osteoarthritis

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 106; no. 4; pp. 1181 - 1186
• Main Authors: Taniguchi, Noboru, Caramés, Beatriz, Ronfani, Lorenza, Ulmer, Ulrich, Komiya, Setsuro, Bianchi, Marco E, Lotz, Martin
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 27.01.2009; National Acad Sciences
• Subjects: Aging; Aging - metabolism; Aging - pathology; Animals; Antibodies; Apoptosis; Arthritis; Articular cartilage; Biological Sciences; Cartilage; Cartilage, Articular - enzymology; Cartilage, Articular - metabolism; Cartilage, Articular - pathology; Cell Survival; Chondrocytes; Chromatin - metabolism; Gene expression; Gene Expression Regulation; HMGB2 Protein - deficiency; HMGB2 Protein - genetics; HMGB2 Protein - metabolism; Humans; Joints; Joints - enzymology; Joints - pathology; Knee joint; Matrix Metalloproteinases - metabolism; Mice; Osteoarthritis; Osteoarthritis - enzymology; Osteoarthritis - metabolism; Osteoarthritis - pathology; Protein Transport; Proteoglycans - metabolism; Rodents
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0806062106

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.