Accumulation of advanced‐glycation end products (AGEs) accelerates arthrogenic joint contracture in immobilized rat knee

Abstract

Joint mobility decreases in the elderly and in diabetics, this process is thought to be caused by accumulation of advanced-glycation end products (AGEs). Here, we aimed to elucidate the role of AGEs in joint contracture formation in rat knees. Rats were injected with ribose or saline into the knees twice weekly for 8 weeks. Pentosidine (AGE) levels were measured in the knee-joint tissues. After serial injections, rats were subjected to unilateral knee-joint immobilization in a flexion position for various periods. At day 21, the passive knee ranges of motions (ROMs) were measured. Knee joint histopathology were assessed, and the expression of fibrotic genes in the posterior joint capsules was examined using real-time PCR. Ribose injection induced a 7.0-fold increase in pentosidine levels relative to saline injection. Joint immobilization resulted in equal myogenic ROM restriction in both groups. Arthrogenic ROM restriction was greater with ribose injection in the immobilized joints (p < 0.05), but was not affected in nonimmobilized joints. Type-I (COL1A1) and type-III (COL3A1) collagen gene expression increased significantly in immobilized joints relative to nonimmobilized joints in the ribose group, but was not affected in the saline group. Ribose injection increased COL1A1 expression slightly and COL3A1 expression significantly in immobilized joints. Histologically, inflammatory changes appeared at day 3 of immobilization and peaked at day 7. These responses trended to be more severe and prolonged in the ribose group than in the saline group. Our data provide evidence for a causal relationship between AGEs and joint contracture formation following immobilization. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:854-863, 2018.

The SOD Mimic, MnTE-2-PyP, Protects from Chronic Fibrosis and Inflammation in Irradiated Normal Pelvic Tissues

“…Upregulation of COL3A1 is frequently correlated with the fibrotic phenotype of the prostate and an active TGF-β1 signaling pathway [ 9 , 10 , 11 ]. Moreover, downregulation of COL3A1, using anti-fibrotic agents, has been correlated with the attenuation of the fibrotic phenotype in different organs [ 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 ]. Therefore, COL3A1 could potentially serve as marker for the fibrotic phenotype in the tissues and organs of the pelvis exposed to radiation.…”

Diabetes mellitus does not increase the risk of knee stiffness after total knee arthroplasty: a meta-analysis of 7 studies including 246 053 cases

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Suppression of TGF-beta activity with remobilization attenuates immobilization-induced joint contracture in rats

“…To assess joint contracture, passive knee extension ROM was measured according to the methods described in the previous study [18]. Brie y, rats were euthanized by carbon dioxide (CO 2 ) inhalation.…”