Abstract

We have determined a role of chondrocyte mitochondrial oxidative phosphorylation (OXPHOS) in matrix synthesis and mineralizing activity. Chondrocyte respiration was inhibited by the NO donor Sin-1. Chondrocyte mitochondrial reserve, as OXPHOS-induced ATP production, supported matrix synthesis and basal and TGFbeta-induced Ppi elaboration, and regulated MV composition and mineralizing activity. Because altered chondrocyte OXPHOS could modulate matrix loss and secondary cartilage mineralization in osteoarthritis (OAO, we propose a limited feasibility study to first assess if experimental OA in rabbit knees can be studied for, and is associated with, mitochondrial OXPHOS impairment. We will also carry out a clinical pilot study to quantify OXPHOS (and identify OXPHOS impairment including deficiency of the mitochondrial protective agent coenzyme Q10 (CoQ10), on an existing panel of isolated primary chondrocytes from human knee OA. Results of this pilot project could determine if OXPHOS preservation is a therapeutic target in OA.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Comprehensive Center (P60)
Project #
5P60AR040770-09
Application #
6310395
Study Section
Special Emphasis Panel (ZAR1-MHG-B (J1))
Project Start
1991-08-01
Project End
2001-02-28
Budget Start
Budget End
Support Year
9
Fiscal Year
2000
Total Cost
$112,459
Indirect Cost

  Institution

Name
University of California San Diego
Department
Type
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093

  Publications

Malcarne, Vanessa L; Hansdottir, Ingunn; McKinney, Ann et al. (2007) Medical signs and symptoms associated with disability, pain, and psychosocial adjustment in systemic sclerosis. J Rheumatol 34:359-67
Leake, John A D; Albani, Salvatore; Kao, Annie S et al. (2004) Acute disseminated encephalomyelitis in childhood: epidemiologic, clinical and laboratory features. Pediatr Infect Dis J 23:756-64
Meyer, Markus; Belke, Darrell D; Trost, Susanne U et al. (2004) A recombinant antibody increases cardiac contractility by mimicking phospholamban phosphorylation. FASEB J 18:1312-4
Groessl, Erik J; Kaplan, Robert M; Cronan, Terry A (2003) Quality of well-being in older people with osteoarthritis. Arthritis Rheum 49:23-8
Kaplan, Robert M (2003) The significance of quality of life in health care. Qual Life Res 12 Suppl 1:3-16
Johnson, Kristen; Goding, James; Van Etten, Deborah et al. (2003) Linked deficiencies in extracellular PP(i) and osteopontin mediate pathologic calcification associated with defective PC-1 and ANK expression. J Bone Miner Res 18:994-1004
La Cava, Antonio; Massa, Margherita; Mendivil, Alberto et al. (2002) Genetic immunization maps T cell (auto)immune responses to self antigens homologous to exogenous proteins. Autoimmunity 35:105-10
Prakken, Berent J; Roord, Sarah; van Kooten, Peter J S et al. (2002) Inhibition of adjuvant-induced arthritis by interleukin-10-driven regulatory cells induced via nasal administration of a peptide analog of an arthritis-related heat-shock protein 60 T cell epitope. Arthritis Rheum 46:1937-46
Kaplan, Robert M (2002) Quality of life: an outcomes perspective. Arch Phys Med Rehabil 83:S44-50
Silverman, Gregg J; Goodyear, Carl S (2002) A model B-cell superantigen and the immunobiology of B lymphocytes. Clin Immunol 102:117-34

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