Abstract
Despite the growing prevalence of post-traumatic osteoarthritis (OA), early and effective treatment options to delay surgical intervention remain limited. Lubricin is a naturally occurring glycoprotein produced by articular chondrocytes and synovial fibroblasts that functions as the principal boundary lubricant in joints. Recently, a recombinant lubricin-like glycoprotein (rhLub) with codon optimized mucin domain was reported to have a sustained residence time (> 6 weeks) following injection into the knee joint of healthy rats. To evaluate outcomes of rhLub injection, skeletally mature Sprague-Dawley rats of both sexes (n = 18) underwent bilateral anterior cruciate ligament transection (ACLT) to initiate post-traumatic OA, followed by three intra-articular injections of 25 µL of rhLub (1.3 mg/mL) or phosphate-buffered saline (PBS) at weekly intervals beginning 1 week post-operatively. Pain sensitization was evaluated weekly throughout the 12-week study with weightbearing and pressure application measurement (PAM). Frontal plane histologic sections of the medial femorotibial joint compartment were scored using Osteoarthritis Research Society International criteria. Injections of rhLub were well-tolerated. rhLub injections protected against cartilage degeneration and improved histologic scores in male rats. Mechanical hyperalgesia and cartilage degeneration scores were greater in female rats compared to males, irrespective of treatment. This study suggests that intra-articular rhLub therapy may be most efficacious in mild-to-moderate disease.
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The datasets generated and/or analyzed during the current study are available from the corresponding author upon request.
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Acknowledgements
The authors acknowledge Lynn Johnson from the Cornell Statistical Consulting Unit (CSCU), the veterinarians and staff at the Center for Animal Resources and Education at Cornell University, Dr. Machiel Ysebaert from the Department of Clinical Sciences in the College of Veterinary Medicine and Biomedical Sciences at Colorado State University, Mary Lou Norman from the Department of Clinical Sciences at the Cornell University College of Veterinary Medicine, and Dr. Soph Ziemian from the Sibley School of Mechanical Engineering at Cornell University. This study was funded by the National Institutes of Health and National Science Foundation through NIH/NIAMS K08AR068469, NIH 3T32AR78751-3S2, and NSF LEAP-HI.
Funding
This study was funded by the National Institutes of Health and National Science Foundation through NIH/NIAMS K08AR068469 (H.L.R.), NIH 3T32AR78751-3S2 (S.J.W.), and NSF LEAP-HI (L.J.B., M.J.P., H.L.R.).
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H.L.R, L.J.B., and M.J.P., conceived the idea, and E.J.S. and H.L.R. designed the animal experiments. S.J.W. and E.J.S. designed and carried out the laboratory experiments, and A.S., M.J.C., S.J.W., S.R.N., and A.G.F. analyzed the data. S.J.W. and H.L.R drafted the manuscript, and all authors reviewed and approved the final version of the manuscript.
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M.J.C., M.J.P., and H.L.R. are named inventors on patents assigned to Cornell University and related to production of recombinant lubricins and mucins. The remaining authors, S.J.W., E.J.S., S.R.N., A.G.F., A.S., and L.J.B., declare no competing interests.
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Womack, S.J., Secor, E.J., Nelissen, S.R. et al. Lubricin protects against cartilage degeneration following anterior cruciate ligament transection in rats. Sci Rep (2026). https://doi.org/10.1038/s41598-026-45349-9
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DOI: https://doi.org/10.1038/s41598-026-45349-9
