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.
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.
|Matsuzaki, Tokio; Alvarez-Garcia, Oscar; Mokuda, Sho et al. (2018) FoxO transcription factors modulate autophagy and proteoglycan 4 in cartilage homeostasis and osteoarthritis. Sci Transl Med 10:|
|Su, Alvin W; Chen, Yunchan; Dong, Yao et al. (2018) Biomechanics of osteochondral impact with cushioning and graft Insertion: Cartilage damage is correlated with delivered energy. J Biomech 73:127-136|
|Abhishek, Abhishek; Neogi, Tuhina; Choi, Hyon et al. (2018) Review: Unmet Needs and the Path Forward in Joint Disease Associated With Calcium Pyrophosphate Crystal Deposition. Arthritis Rheumatol 70:1182-1191|
|Fisch, K M; Gamini, R; Alvarez-Garcia, O et al. (2018) Identification of transcription factors responsible for dysregulated networks in human osteoarthritis cartilage by global gene expression analysis. Osteoarthritis Cartilage 26:1531-1538|
|Ramdani, Ghania; Schall, Nadine; Kalyanaraman, Hema et al. (2018) cGMP-dependent protein kinase-2 regulates bone mass and prevents diabetic bone loss. J Endocrinol 238:203-219|
|Serrano, Ramon L; Chen, Liang-Yu; Lotz, Martin K et al. (2018) Impaired Proteasomal Function in Human Osteoarthritic Chondrocytes Can Contribute to Decreased Levels of SOX9 and Aggrecan. Arthritis Rheumatol 70:1030-1041|
|Jin, Yunyun; Cong, Qian; Gvozdenovic-Jeremic, Jelena et al. (2018) Enpp1 inhibits ectopic joint calcification and maintains articular chondrocytes by repressing hedgehog signaling. Development 145:|
|Grogan, Shawn P; Duffy, Stuart F; Pauli, Chantal et al. (2018) Gene expression profiles of the meniscus avascular phenotype: A guide for meniscus tissue engineering. J Orthop Res 36:1947-1958|
|Baek, Jihye; Sovani, Sujata; Choi, Wonchul et al. (2018) Meniscal Tissue Engineering Using Aligned Collagen Fibrous Scaffolds: Comparison of Different Human Cell Sources. Tissue Eng Part A 24:81-93|
|Chen, L-Y; Wang, Y; Terkeltaub, R et al. (2018) Activation of AMPK-SIRT3 signaling is chondroprotective by preserving mitochondrial DNA integrity and function. Osteoarthritis Cartilage 26:1539-1550|
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