title: Progressive cell-mediated changes in articular cartilage and bone in mice are initiated by a single session of controlled cyclic compressive loading.
abstract: We previously showed that repetitive cyclic loading of the mouse knee joint causes changes that recapitulate the features of osteoarthritis (OA) in humans. By applying a single loading session, we characterized the temporal progression of the structural and compositional changes in subchondral bone and articular cartilage. We applied loading during a single 5-minute session to the left tibia of adult (26-week-old) C57Bl/6 male mice at a peak load of 9.0N for 1,200 cycles. Knee joints were collected at times 0, 1, and 2 weeks after loading. The changes in articular cartilage and subchondral bone were analyzed by histology, immunohistochemistry (caspase-3 and cathepsin K), and microcomputed tomography. At time 0, no change was evident in chondrocyte viability or cartilage or subchondral bone integrity. However, cartilage pathology demonstrated by localized thinning and proteoglycan loss occurred at 1 and 2 weeks after the single session of loading. Transient cancellous bone loss was evident at 1 week, associated with increased osteoclast number. Bone loss was reversed to control levels at 2 weeks. We observed formation of fibrous and cartilaginous tissues at the joint margins at 1 and 2 weeks. Our findings demonstrate that a single session of noninvasive loading leads to the development of OA-like morphological and cellular alterations in articular cartilage and subchondral bone. The loss in subchondral trabecular bone mass and thickness returns to control levels at 2 weeks, whereas the cartilage thinning and proteoglycan loss persist. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1941-1949, 2016.
authors.affiliation: Meinig School of Biomedical Engineering, Sibley School of Mechanical and Aerospace Engineering, Cornell University, 219 Upson Hall, Ithaca, New York 14853.
authors.forename: Frank C
authors.initials: FC
authors.lastname: Ko
authors.affiliation: Research Division, Hospital for Special Surgery, New York, New York.
authors.forename: Cecilia L
authors.initials: CL
authors.lastname: Dragomir
authors.affiliation: Research Division, Hospital for Special Surgery, New York, New York.
authors.forename: Darren A
authors.initials: DA
authors.lastname: Plumb
authors.affiliation: Meinig School of Biomedical Engineering, Sibley School of Mechanical and Aerospace Engineering, Cornell University, 219 Upson Hall, Ithaca, New York 14853.
authors.forename: Allison W
authors.initials: AW
authors.lastname: Hsia
authors.affiliation: Meinig School of Biomedical Engineering, Sibley School of Mechanical and Aerospace Engineering, Cornell University, 219 Upson Hall, Ithaca, New York 14853.
authors.forename: Olufunmilayo O
authors.initials: OO
authors.lastname: Adebayo
authors.affiliation: Research Division, Hospital for Special Surgery, New York, New York.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Goldring
authors.affiliation: Research Division, Hospital for Special Surgery, New York, New York.
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Wright
authors.affiliation: Research Division, Hospital for Special Surgery, New York, New York.
authors.forename: Mary B
authors.initials: MB
authors.lastname: Goldring
authors.affiliation: Meinig School of Biomedical Engineering, Sibley School of Mechanical and Aerospace Engineering, Cornell University, 219 Upson Hall, Ithaca, New York 14853.|Research Division, Hospital for Special Surgery, New York, New York.
authors.forename: Marjolein C H
authors.initials: MC
authors.lastname: van der Meulen
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D001842:Bone and Bones / Q000502:physiology*; D002358:Cartilage, Articular / Q000502:physiology*; D008297:Male; D008810:Mice, Inbred C57BL; D020370:Osteoarthritis, Knee / Q000209:etiology*; D054850:Osteophyte / Q000209:etiology; D013583:Synovial Membrane / Q000502:physiology; D016474:Weight-Bearing
keywords: bone resorption; chondrocytes; mechanical loading; mouse; osteoarthritis