Our previous studies of the epiphyseal growth cartilage have served to focus attention on the relationship between oxidative metabolism and the initiation of mineralization. These studies showed that aside from normal respiratory activities there was evidence of non-mitochondrial oxidative metabolism. Moreover, preliminary investigations indicated that there was evidence of shunt activity and lipid peroxidation in the growth cartilage. In skeletal and dental tissues, a developmental role for the abrupt changes in oxidative metabolism documented during chondrocyte maturation and subsequent mineralization is postulated. The proposed experiments examine the status of non-mitochondrial oxygen metabolism both in situ in the growth plate and in vitro employing a mineralizing chondrocyte culture system. In particular, this study focuses on mechanisms of matrix vesicle biogenesis and expression of collagenous and non-collagenous proteins in relationship to non-mitochondrial oxidative metabolism.
Four Specific Aims are proposed. The first is to map lipid peroxidation and oxygen radical degradation in the growth plate in relationship to maturation of the chondrocyte. Second, we will explore the effects of lipid peroxidation on matrix vesicle biogenesis in cultured chondrocytes. The third Specific Aim will examine the impact of oxygen radical species on expression and function of collagenous and non-collagenous proteins. Finally, the last Specific Aim will probe a possible mechanism for matrix vesicle biogenesis implicating non-mitochondrial oxidative metabolism in the selection of chondrocyte membrane segments for vesiculation.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE009684-03
Application #
3223477
Study Section
Oral Biology and Medicine Subcommittee 1 (OBM)
Project Start
1991-02-15
Project End
1996-02-14
Budget Start
1993-02-15
Budget End
1994-02-14
Support Year
3
Fiscal Year
1993
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Type
Schools of Dentistry
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Teixeira, Cristina C; Ischiropoulos, Harry; Leboy, Phoebe S et al. (2005) Nitric oxide-nitric oxide synthase regulates key maturational events during chondrocyte terminal differentiation. Bone 37:37-45
Teixeira, Cristina C; Rajpurohit, Ramesh; Mansfield, Kyle et al. (2003) Maturation-dependent thiol loss increases chondrocyte susceptibility to apoptosis. J Bone Miner Res 18:662-8
Ohyama, K; Farquharson, C; Whitehead, C C et al. (1997) Further observations on programmed cell death in the epiphyseal growth plate: comparison of normal and dyschondroplastic epiphyses. J Bone Miner Res 12:1647-56
Hung, C T; Allen, F D; Mansfield, K D et al. (1997) Extracellular ATP modulates [Ca2+]i in retinoic acid-treated embryonic chondrocytes. Am J Physiol 272:C1611-7
Teixeira, C C; Shapiro, I M; Hatori, M et al. (1996) Retinoic acid modulation of glutathione and cysteine metabolism in chondrocytes. Biochem J 314 ( Pt 1):21-6
Hatori, M; Klatte, K J; Teixeira, C C et al. (1995) End labeling studies of fragmented DNA in the avian growth plate: evidence of apoptosis in terminally differentiated chondrocytes. J Bone Miner Res 10:1960-8
Teixeira, C C; Hatori, M; Leboy, P S et al. (1995) A rapid and ultrasensitive method for measurement of DNA, calcium and protein content, and alkaline phosphatase activity of chondrocyte cultures. Calcif Tissue Int 56:252-6
Abreu, S; Hayden, J; Berthold, P et al. (1995) Growth plate pathology in feline mucopolysaccharidosis VI. Calcif Tissue Int 57:185-90
Hatori, M; Sparkman, J; Teixeira, C C et al. (1995) Effects of deferoximine on chondrocyte alkaline phosphatase activity: proxidant role of deferoximine in thalassemia. Calcif Tissue Int 57:229-36
Shapiro, I M; Debolt, K; Hatori, M et al. (1994) Retinoic acid induces a shift in the energetic state of hypertrophic chondrocytes. J Bone Miner Res 9:1229-37

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