Daily oral consumption of hydrolyzed type 1 collagen is chondroprotective and anti-inflammatory in murine posttraumatic osteoarthritis

Abstract

Osteoarthritis (OA) is a degenerative joint disease for which there are no disease modifying therapies. Thus, strategies that offer chondroprotective or regenerative capability represent a critical unmet need. Recently, oral consumption of a hydrolyzed type 1 collagen (hCol1) preparation has been reported to reduce pain in human OA and support a positive influence on chondrocyte function. To evaluate the tissue and cellular basis for these effects, we examined the impact of orally administered hCol1 in a model of posttraumatic OA (PTOA). In addition to standard chow, male C57BL/6J mice were provided a daily oral dietary supplement of hCol1 and a meniscal-ligamentous injury was induced on the right knee. At various time points post-injury, hydroxyproline (hProline) assays were performed on blood samples to confirm hCol1 delivery, and joints were harvested for tissue and molecular analyses were performed, including histomorphometry, OARSI and synovial scoring, immunohistochemistry and mRNA expression studies. Confirming ingestion of the supplements, serum hProline levels were elevated in experimental mice administered hCol1. In the hCol1 supplemented mice, chondroprotective effects were observed in injured knee joints, with dose-dependent increases in cartilage area, chondrocyte number and proteoglycan matrix at 3 and 12 weeks post-injury. Preservation of cartilage and increased chondrocyte numbers correlated with reductions in MMP13 protein levels and apoptosis, respectively. Supplemented mice also displayed reduced synovial hyperplasia that paralleled a reduction in Tnf mRNA, suggesting an anti-inflammatory effect. These findings establish that in the context of murine knee PTOA, daily oral consumption of hCol1 is chondroprotective, anti-apoptotic in articular chondrocytes, and anti-inflammatory. While the underlying mechanism driving these effects is yet to be determined, these findings provide the first tissue and cellular level information explaining the already published evidence of symptom relief supported by hCol1 in human knee OA. These results suggest that oral consumption of hCol1 is disease modifying in the context of PTOA.

Chondrocyte-Specific RUNX2 Overexpression Accelerates Post-traumatic Osteoarthritis Progression in Adult Mice

“…This surgery combines transection of the MCL and excision of a piece of the anteromedial meniscus, which induces a progressive OA‐like phenotype resulting in complete loss of cartilage by 20 weeks postinjury . The MLI is a model of partial meniscectomy, an event known to increase the risk of OA development in humans, and we use it routinely with consistent results in mice . Compared to the more widely used destabilized medial meniscus (DMM) surgery where transection of the medial meniscotibial ligament induces joint instability, OA following MLI progresses at a slightly accelerated rate.…”

“…(19,36) The MLI is a model of partial meniscectomy, an event known to increase the risk of OA development in humans, and we use it routinely with consistent results in mice. (31,53,54) Compared to the more widely used destabilized medial meniscus (DMM) surgery where transection of the medial meniscotibial ligament induces joint instability, OA following MLI progresses at a slightly accelerated rate. Although we did find statistically significant differences using the MLI, it is possible that the magnitude of these differences could have been greater had we used a less aggressive model of PTOA such as the DMM.…”

Attenuated Joint Tissue Damage Associated With Improved Synovial Lymphatic Function Following Treatment With Bortezomib in a Mouse Model of Experimental Posttraumatic Osteoarthritis

“…It may affect lymphatics systemically. This is unlikely, however, because this antibody mainly blocks newly formed lymphatic vessels, such as in tumor‐induced () and inflammation‐induced lymphangiogenesis in mice. We did not find swelling or increased body weight in VEGFR‐3 antibody–treated mice.…”

“…The mean score for the 3 levels from each observer was calculated, and the mean score from all 4 individual observers was then used. Interrater agreement for each score was evaluated by calculating the Fleiss kappa coefficient . The results indicated that there was no significant interobserver variation (data not shown).…”

Gelatin versus its two major degradation products, prolyl‐hydroxyproline and glycine, as supportive therapy in experimental colitis in mice

“…Collagen is the most abundant animal protein, and accounts for about 30% of total protein in both vertebrates and invertebrates (Liu, Nikoo, Boran, Zhou, & Regenstein, ). Collagen peptides have been reported to be anti‐inflammatory against osteoarthritis, burn injury, skin inflammation, and ulcerative colitis (Azuma, Osaki, Itoh, Arifuku, & Okamoto, ; Chen, Hou, Wang, Zhao, & Li, ; Dar et al., ; Hartog, Cozijnsen, de Vrij, & Garssen, ). However, collagen‐rich animal tissues such as skin, tendon, and cartilage are largely excluded from the modern diet, which typically includes a great deal of processed meat.…”