Qurratul-Ain Dar1,2☯, Eric M. Schott1,3☯, Sarah E. Catheline1,3☯, Robert D. Maynard1,3, Zhaoyang Liu1, Fadia Kamal1,4, Christopher W. Farnsworth1,3, John P. Ketz1,4, Robert A. Mooney1,3, Matthew J. Hilton5, Jennifer H. Jonason1,4, Janne Prawitt6, Michael
J. Zuscik1,4*

1 Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, New York, United States of America, 2 Department of Biology, University of Rochester, Rochester, New York, United States of America, 3 Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, New York, United States of America, 4 Department of Orthopaedics & Rehabilitation, University of Rochester Medical Center, Rochester, New York, United States of America, 5 Orthopaedic Cellular, Developmental & Genome Laboratories, Duke University, Durham, North Carolina, United States of America, 6 Rousselot BVBA, Gent, Belgium

☯ These authors contributed equally to this work. * michael_zuscik@urmc.rochester.edu


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 supple- ment 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, immunohistochemis- try 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 chon- drocytes, 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.

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