This study investigated whether oral supplementation with protease-soluble chicken type II collagen (PSCC-II) mitigates the progression of anterior cruciate ligament transection (ACLT)–induced osteoarthritis (OA) in rats. Eight-week-old male Wistar rats were randomly assigned to the following groups: control, sham, ACLT, group A (ACLT + pepsin-soluble collagen type II collagen (C-II) with type I collagen), group B (ACLT + Amano M–soluble C-II with type I collagen), group C (ACLT + high-dose Amano M–soluble C-II with type I collagen), and group D (ACLT + unproteolyzed C-II). Various methods were employed to analyze the knee joint: nociceptive tests, microcomputed tomography, histopathology, and immunohistochemistry. Rats treated with any form of C-II had significant reductions in pain sensitivity and cartilage degradation. Groups that received PSCC-II treatment effectively mitigated the ACLT-induced effects of OA concerning cancellous bone volume, trabecular number, and trabecular separation compared with the ACLT alone group. Furthermore, PSCC-II and unproteolyzed C-II suppressed ACLT-induced effects, such as the downregulation of C-II and upregulation of matrix metalloproteinase-13, tumor necrosis factor-α, and interleukin-1β. These results indicate that PSCC-II treatment retains the protective effects of traditional undenatured C-II and provide superior benefits for OA management. These benefits encompass pain relief, anti-inflammatory effects, and the protection of cartilage and cancellous bone.
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