The overall goal of this project is to elucidate mechanobiological mechanisms and consequences of functional deterioration of articular cartilage, leading to partial-thickness erosions in the human knee in aging and osteoarthritis. Biomechanical abnormalities occur in the superficial zone of articular cartilage during normal aging, and this is associated with an increased incidence of osteoarthritis. The overall hypothesis is that the superficial zone of normal human knee articular cartilage undergoes aging-related mechanobiolgoical decompensation due to both cell and matrix dysfunction, with a resultant compromise in both cartilage lubrication and load-bearing properties. To address this hypothesis, we propose to test the following aims: 1) Analyze human and mouse knees for spatial signatures of biomechanical dysfunction or failure of the articular cartilage, and the relationship of such variation to putative determinants, matrix composition and structure and also cell organization and phenotype;2) Determine if in vitro dynamic loading of cartilage explants in compression and shear cause cell responses and matrix remodeling in the superficial zone that lead to aging-related compromise of cartilage lubrication and load-bearing functions.

Public Health Relevance

Completion of the proposed studies will help elucidate the mechanobiological cascade contributing to the age- and osteoarthritis-related deterioration of articular cartilage. Such an understanding may facilitate the development of new interventions to forestell the incidence of osteoarthritis.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Program Projects (P01)
Project #
Application #
Study Section
Special Emphasis Panel (ZAG1)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Scripps Research Institute
La Jolla
United States
Zip Code
Meckes, J K; Caram├ęs, B; Olmer, M et al. (2017) Compromised autophagy precedes meniscus degeneration and cartilage damage in mice. Osteoarthritis Cartilage 25:1880-1889
Hasei, Joe; Teramura, Takeshi; Takehara, Toshiyuki et al. (2017) TWIST1 induces MMP3 expression through up-regulating DNA hydroxymethylation and promotes catabolic responses in human chondrocytes. Sci Rep 7:42990
Mouser, Vivian H M; Levato, Riccardo; Bonassar, Lawrence J et al. (2017) Three-Dimensional Bioprinting and Its Potential in the Field of Articular Cartilage Regeneration. Cartilage 8:327-340
Shen, T; Alvarez-Garcia, O; Li, Y et al. (2017) Suppression of Sestrins in aging and osteoarthritic cartilage: dysfunction of an important stress defense mechanism. Osteoarthritis Cartilage 25:287-296
He, Sha; Johnson, Noah J J; Nguyen Huu, Viet Anh et al. (2017) Simultaneous Enhancement of Photoluminescence, MRI Relaxivity, and CT Contrast by Tuning the Interfacial Layer of Lanthanide Heteroepitaxial Nanoparticles. Nano Lett 17:4873-4880
Alvarez-Garcia, Oscar; Matsuzaki, Tokio; Olmer, Merissa et al. (2017) Age-related reduction in the expression of FOXO transcription factors and correlations with intervertebral disc degeneration. J Orthop Res 35:2682-2691
Akagi, R; Akatsu, Y; Fisch, K M et al. (2017) Dysregulated circadian rhythm pathway in human osteoarthritis: NR1D1 and BMAL1 suppression alters TGF-? signaling in chondrocytes. Osteoarthritis Cartilage 25:943-951
Hasegawa, Akihiko; Yonezawa, Tomo; Taniguchi, Noboru et al. (2017) Role of Fibulin 3 in Aging-Related Joint Changes and Osteoarthritis Pathogenesis in Human and Mouse Knee Cartilage. Arthritis Rheumatol 69:576-585
Asahara, Hiroshi; Inui, Masafumi; Lotz, Martin K (2017) Tendons and Ligaments: Connecting Developmental Biology to Musculoskeletal Disease Pathogenesis. J Bone Miner Res 32:1773-1782
Kalyanaraman, Hema; Ramdani, Ghania; Joshua, Jisha et al. (2017) A Novel, Direct NO Donor Regulates Osteoblast and Osteoclast Functions and Increases Bone Mass in Ovariectomized Mice. J Bone Miner Res 32:46-59

Showing the most recent 10 out of 303 publications