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Collagen XI mutation lowers susceptibility to load-induced cartilage damage in mice.
- Source :
-
Journal of orthopaedic research : official publication of the Orthopaedic Research Society [J Orthop Res] 2018 Feb; Vol. 36 (2), pp. 711-720. Date of Electronic Publication: 2017 Oct 31. - Publication Year :
- 2018
-
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.<br /> (© 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)
- Subjects :
- Animals
Cancellous Bone anatomy & histology
Cortical Bone anatomy & histology
Male
Mice, Inbred C57BL
Osteophyte etiology
Phenotype
Point Mutation
Tibia physiology
Weight-Bearing
Cancellous Bone physiology
Cartilage, Articular abnormalities
Collagen Type XI genetics
Cortical Bone physiology
Osteoarthritis genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1554-527X
- Volume :
- 36
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Journal of orthopaedic research : official publication of the Orthopaedic Research Society
- Publication Type :
- Academic Journal
- Accession number :
- 28898438
- Full Text :
- https://doi.org/10.1002/jor.23731