title: Mechanics of chondrocyte hypertrophy.
abstract: Chondrocyte hypertrophy is a characteristic of osteoarthritis and dominates bone growth. Intra- and extracellular changes that are known to be induced by metabolically active hypertrophic chondrocytes are known to contribute to hypertrophy. However, it is unknown to which extent these mechanical conditions together can be held responsible for the total magnitude of hypertrophy. The present paper aims to provide a quantitative, mechanically sound answer to that question. To address this aim requires a quantitative tool that captures the mechanical effects of collagen and proteoglycans, allows temporal changes in tissue composition, and can compute cell and tissue deformations. These requirements are met in our numerical model that is validated for articular cartilage mechanics, which we apply to quantitatively explain a range of experimental observations related to hypertrophy. After validating the numerical approach for studying hypertrophy, the model is applied to evaluate the direct mechanical effects of axial tension and compression on hypertrophy (Hueter-Volkmann principle) and to explore why hypertrophy is reduced in case of partially or fully compromised proteoglycan expression. Finally, a mechanical explanation is provided for the observation that chondrocytes do not hypertrophy when enzymatical collagen degradation is prohibited (S1Pcko knock-out mouse model). This paper shows that matrix turnover by metabolically active chondrocytes, together with externally applied mechanical conditions, can explain quantitatively the volumetric change of chondrocytes during hypertrophy. It provides a mechanistic explanation for the observation that collagen degradation results in chondrocyte hypertrophy, both under physiological and pathological conditions.
authors.affiliation: Department of Biomedical Engineering, Eindhoven University of Technology, 5600 MB, Eindhoven, The Netherlands. c.c.v.donkelaar@tue.nl
authors.forename: C C
authors.initials: CC
authors.lastname: van Donkelaar
authors.forename: W
authors.initials: W
authors.lastname: Wilson
mesh_terms: D000818:Animals; D019902:Chondrocytes / Q000378:metabolism / Q000473:pathology*; D003094:Collagen / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D020342:Finite Element Analysis; D006984:Hypertrophy; D051379:Mice
chemical_list: D003094:Collagen