Harry C. Blair, M.D., Professor
E-mail: hcblair@imap.pitt.edu
Research Interests:
Dr. Blair's current research activity is centered on:
- The role of calmodulin and cGMP in osteoclast control. This work considers how Ca+2 interacts with cGMP, itself modified by NO. Goals: 1) Determine the physiological role of intracellular calcium puffs at the acid secretion site. 2) Modify production of cGMP-dependent protein kinase or calmodulin-dependent phosphatase and study the effects on osteoclastic activity. 3) Characterize the interaction of cGMP and Ca+2 signals in osteoclasts. NIH 1RO1 AG12951-05; 99-00 direct $161,935.
- Phytoestrogen regulation of bone turnover. We are studying which cells in bone turnover respond to estrogens, and the receptor(s) that mediate this response. Goals: 1) Determine the response of osteoclast regulatory proteins to isoflavone SERMs. 2) Assess the activity of isoflavones when ERs are eliminated. 3) Characterize ER-independent actions of isoflavones in osteoclast membranes. AR 46587-01 2000-01 direct $142,553.
- Regulation of osteoclasts in hyperparathyroid bone. This work is considering how cytokines expressed in response to PTH, notably a membrane form of the kit ligand, m-SCF, interact with basal signals for osteoclast formation. Its goals are to: 1) Characterize the interactions of m-SCF, CSF-1, and RANK-ligand in osteoclast formation. 2) Determine how m-SCF functions in ectopic mast cell and alternative osteoclast development. Department of Veterans Affair's Merit Award; current year $110,000 direct costs.
- Downregulation of osteoclastic activity. This project is in development, and includes studies considering key mechanisms affecting human bone turnover related to major disease states. It will determine the relative roles of apoptotic and reversible mechanisms in regulation of bone degradation by 1) glucocorticoids, via receptors in (pre) osteoclastic and osteoblastic cells; and 2) bone-associated pH eluted antimetabolites, via interference with osteoclastic secretory mechanisms or osteoblastic differentiation/activation signals.
Selected Publications:
Eberhardt AW, Yeager-Jones A, Blair HC. Regional trabecular bone matrix degeneration and osteocyte death in femora of glucocorticoid treated rabbits. Endocrinology 142: 1333-1340, 2001.
Blair HC, Zaidi M, Schlesinger PH. Mechanisms Balancing Skeletal Matrix Synthesis and Degradation. Biochem J 364: 329-341, 2002.
Cao L, Bu R Oakley JI, Kalla SE, Blair HC. Estrogen Receptor-b Modifies Expression of Matrix Proteins in Human MG63 Osteosarcoma Cells. J Cell Biochem 89, 152-164, 2003.
Wu X-B, Li Y, Schneider A, Yu W, Rajendren G, Yamamoto M, Alam M, Brunet LJ, Harland RM, Blair HC, Zaidi M, Abe E. Impaired osteoblastic differentiation, reduced bone formation and severe osteoporosis in noggin overexpressing mice reveal new insights into the pathogenesis of involutional osteoporosis. J Clin Invest 112: 924-34, 2003.
Bu R, Borysenko CW, Li Y Sabokbar, A, Blair HC. Expression of TNF-family proteins and Receptors in Human Osteoblasts. Bone 33: 760-770, 2003.
Abe E, Marians RC, Wu X-B, Iqbal J, Ando T, Li Y, Blair HC, Davies TF, Zaidi M. TSH is a Negative Regulator of Skeletal Remodeling. Cell 115: 151-162, 2003.
Yaroslavskiy BB, Li Y, Ferguson DJP, Kalla SE, Oakley JI, Blair HC. Autocrine and Paracrine Nitric Oxide Regulate Attachment of Human Osteoclasts. J Cell Biochem 91: 962-972, 2004.
Glading A, Bodnar R, Reynolds IJ, Shiraha H, Satish L, Potter DA, Blair HC, Wells A. EGF activates m-calpain, at least in part, by Extracellular Signal-Regulated Kinase-Mediated Phosphorylation. Mol Cell Biol 24: 2499-512, 2004.
Blair HC, Borysenko CW, Villa A, Schlesinger PH, Kalla SE, Yaroslavskiy BB, Garcia-Palacios V, Oakley JI, Orchard PJ. In Vitro Differentiation of CD14 Cells From Osteopetrotic Subjects: Contrasting Phenotypes With TCIRG1, CLCN7, and Attachment Defects. J Bone Miner Res. 19: 1329-38, 2004.
