Naked mole‐rats are extremely resistant to post‐traumatic osteoarthritis. Issue 11 (28th October 2020)

• Record Type: Journal Article
• Authors: Taguchi, Taketo; Kotelsky, Alexander; Takasugi, Masaki; Chang, Martin; Ke, Zhonghe; Betancourt, Megan; Buckley, Mark R.; Zuscik, Michael; Seluanov, Andrei; Gorbunova, Vera
• Is Part Of: Aging cell. Volume 19:Issue 11(2020)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-10-28
• Subjects: aging -- naked mole rat -- ostheoarthritis; Cells -- Aging -- Periodicals; 571.8783605
• DOI: 10.1111/acel.13255
• Languages: English
• ISSNs: 1474-9718

Abstract

Abstract: Osteoarthritis (OA) is the most prevalent disabling disease, affecting quality of life and contributing to morbidity, particularly during aging. Current treatments for OA are limited to palliation: pain management and surgery for end‐stage disease. Innovative approaches and animal models are needed to develop curative treatments for OA. Here, we investigated the naked mole‐rat (NMR) as a potential model of OA resistance. NMR is a small rodent with the maximum lifespan of over 30 years, resistant to a wide range of age‐related diseases. NMR tissues accumulate large quantities of unique, very high molecular weight, hyaluronan (HA). HA is a major component of cartilage and synovial fluid. Importantly, both HA molecular weight and cartilage stiffness decline with age and progression of OA. As increased polymer length is known to result in stiffer material, we hypothesized that NMR high molecular weight HA contributes to stiffer cartilage. Our analysis of biomechanical properties of NMR cartilage revealed that it is significantly stiffer than mouse cartilage. Furthermore, NMR chondrocytes were highly resistant to traumatic damage. In vivo experiments using an injury‐induced model of OA revealed that NMRs were highly resistant to OA. While similarly treated mice developed severe cartilage degeneration, NMRs did not show any signs of OA. Our study shows that NMRs are remarkably resistant to OA, and this resistance is likely conferred by high molecular weight HA. This work suggests that NMR is a useful model to study OA resistance and NMR high molecular weight HA may hold therapeutic potential for OA treatment. Abstract : Naked mole‐rats are remarkably resistant to post‐traumatic osteoarthritis. Their cartilage is stiffer than mouse cartilage and better protects chondrocytes from damage. These unique biomechanical properties of the naked mole‐rat cartilage are likely due to abundant high molecular weight hyaluronan present in the naked mole‐rat joints.