In the proposed studies four aspects of osteoclast structure and function will be investigated. First, the function of several enzymes, two located at the ruffled border (Na,K-ATPase, H-ATPase) and one situated on the plasma membrane of the opposite side of the cell (Ca-ATPase), will be studied using enzyme activity assays and studies of ion-translocation into vesicles derived from osteoclast plasma membrane. Second, sites of acidity in and under osteoclasts at the ultrastructural level will be investigated. Third, studies of the distribution of cytoskeletal elements and the influence of calcium-regulating hormones on them will be continued. Of particular interest are the actin-associating proteins which link cytoskeletal elements to various organelles, including the plasma membrane. Immunoblotting, immunofluorescence, and ultrastructural immunocytochemistry will be employed. Fourth, the presence and distribution of calmodulin in osteoclasts will be studied. There are many calmodulin-regulated functions in cells, and it is important to establish its sites of action in osteoclasts. The several aspects of osteoclast structure, composition, and function we propose to investigate should provide further information for establishing a more rational basis in designing therapeutic measures directed at metabolic diseases of the skeleton.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE004345-14
Application #
3219039
Study Section
Oral Biology and Medicine Study Section (OBM)
Project Start
1976-04-01
Project End
1991-06-30
Budget Start
1989-07-01
Budget End
1990-06-30
Support Year
14
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Pennsylvania State University
Department
Type
Schools of Arts and Sciences
DUNS #
City
University Park
State
PA
Country
United States
Zip Code
16802
Brubaker, K D; Mao, F; Gay, C V (1999) Localization of carbonic anhydrase in living osteoclasts with bodipy 558/568-modified acetazolamide, a thiadiazole carbonic anhydrase inhibitor. J Histochem Cytochem 47:545-50
Brubaker, K D; Gay, C V (1999) Evidence for plasma membrane-mediated effects of estrogen. Calcif Tissue Int 64:459-62
Brubaker, K D; Gay, C V (1999) Depolarization of osteoclast plasma membrane potential by 17beta-estradiol. J Bone Miner Res 14:1861-6
Brubaker, K D; Gay, C V (1999) Estrogen stimulates protein tyrosine phosphorylation and Src kinase activity in avian osteoclasts. J Cell Biochem 76:206-16
Hunter, S J; Gay, C V; Osdoby, P A et al. (1998) Spectrin localization in osteoclasts: immunocytochemistry, cloning, and partial sequencing. J Cell Biochem 71:204-15
May, L G; Gay, C V (1997) Multiple G-protein involvement in parathyroid hormone regulation of acid production by osteoclasts. J Cell Biochem 64:161-70
May, L G; Gay, C V (1997) Parathyroid hormone uses both adenylate cyclase and protein kinase C to regulate acid production in osteoclasts. J Cell Biochem 65:565-73
Gay, C V (1996) Role of microscopy in elucidating the mechanism and regulation of the osteoclast resorptive apparatus. Microsc Res Tech 33:165-70
May, L G; Gay, C V (1996) Development of a new method for obtaining osteoclasts from endosteal surfaces. In Vitro Cell Dev Biol Anim 32:269-78
Brubaker, K D; Gay, C V (1994) Specific binding of estrogen to osteoclast surfaces. Biochem Biophys Res Commun 200:899-907

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