Tissue stiffness induced by prolonged immobilization of the rat knee joint and relevance of AGEs (pentosidine)

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Joints, connective tissues consisting of extracellular matrix (ECM) with few blood vessels, transfer tension to the skeleton in response to environmental demand. Therefore, joint immobilization decreases active and passive mechanical stress, resulting in increased joint stiffness and tissue degeneration; however, the cause of joint stiffness is obscure. Using a rat knee immobilization model, we examined the relationship between range of motion (ROM) and cell numbers and ECM cross-links by accumulation of advanced glycation end products, pentosidine, in the posterior joint capsule of immobilized joints during 16 weeks of immobilization. The left knee joint was immobilized by internal fixation and compared with the non-immobilized right leg. As early as 2 weeks of immobilization, joint ROM and torque significantly decreased and in parallel, disordered alignment of collagen fiber bundles significantly increased, compared with non-immobilized joints. Those changes continued until 16 weeks of immobilization. Significant increases in pentosidine-positive areas after 8 weeks and significantly decreased cell numbers after 16 weeks of immobilization were also observed compared to the contralateral side. A significant negative correlation between tissue stiffness measured by restriction of ROM and accumulation of pentosidine was observed. This study is the first to show that immobilization of knee joints induces articular contracture associated with sequential changes of ECM alignment, influencing ROM and later pentosidine accumulation and decreased cell numbers during the 16-week immobilization period. Pentosidine appears to be an indicator toward a chronic tissue stiffness leading to decreased cell number rather than a cause of ROM restriction induced by joint immobilization.