Collagen XI mutation lowers susceptibility to load‐induced cartilage damage in mice. Issue 2 (31st October 2017)

• Record Type: Journal Article
• Authors: Holyoak, Derek T.; Otero, Miguel; Armar, Naa Shidaa; Ziemian, Sophia N.; Otto, Ariana; Cullinane, Devinne; Wright, Timothy M.; Goldring, Steven R.; Goldring, Mary B.; van der Meulen, Marjolein C. H.
• Is Part Of: Journal of orthopaedic research. Volume 36:Issue 2(2018)
• Page Start: 711
• Page End: 720
• Publication Date: 2017-10-31
• Subjects: osteoarthritis -- mechanical loading -- Col11a1 haploinsufficiency -- abnormal matrix properties -- bone; Orthopedics -- Periodicals; Musculoskeletal system -- Periodicals; 616.7
• DOI: 10.1002/jor.23731
• Languages: English
• ISSNs: 0736-0266

Abstract

ABSTRACT: Interactions among risk factors for osteoarthritis (OA) are not well understood. We investigated the combined impact of two prevalent risk factors: mechanical loading and genetically abnormal cartilage tissue properties. We used cyclic tibial compression to simulate mechanical loading in the cho/+ ( Col11a1 haploinsufficient) mouse, which has abnormal collagen fibrils in cartilage due to a point mutation in the Col11a1 gene. We hypothesized that the mutant collagen would not alter phenotypic bone properties and that cho/+ mice, which develop early onset OA, would develop enhanced load‐induced cartilage damage compared to their littermates. To test our hypotheses, we applied cyclic compression to the left tibiae of 6‐month‐old cho/+ male mice and wild‐type (WT) littermates for 1, 2, and 6 weeks at moderate (4.5 N) and high (9.0 N) peak load magnitudes. We then characterized load‐induced cartilage and bone changes by histology, microcomputed tomography, and immunohistochemistry. Prior to loading, cho/+ mice had less dense, thinner cortical bone compared to WT littermates. In addition, in loaded and non‐loaded limbs, cho/+ mice had thicker cartilage. With high loads, cho/+ mice experienced less load‐induced cartilage damage at all time points and displayed decreased matrix metalloproteinase (MMP)‐13 levels compared to WT littermates. The thinner, less dense cortical bone and thicker cartilage were unexpected and may have contributed to the reduced severity of load‐induced cartilage damage in cho/+ mice. Furthermore, the spontaneous proteoglycan loss resulting from the mutant collagen XI was not additive to cartilage damage from mechanical loading, suggesting that these risk factors act through independent pathways. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:711–720, 2018.