Congenital skeletal anomalies such as infantile malignant osteopetrosis and craniometaphyseal dysplasia potentially arise from genetic bone lesions or epigenetic events. Bone forming osteoblasts, bone resorbing osteoclasts, and/or their precursor cells may be affected. Craniofacial reconstruction is dependent on host graft interaction to induce new bone formation. The composition of the bone graft is important to elicit net bone deposition as opposed to net bone resorption. Relatively little is known about the complex genetic and epigenetic factors that regular bone development and remodelling. The proposed studies are intended to provide detailed information about the interactions between bone cells, bone cell precursor populations, and extracellular matrices. Local and systemic signals apparently interface with the genetic program to orchestrate precise bone modeling. The cellular basis of this interaction is unknown. Isolated osteoclasts and monocyte derived multinucleated giant cells will be exploited to investigate osteoclast differentiation and function in vitro. In addition an osteoblast differentiation system will be used to investigate osteoblast-osteoclast interactions in vitro. Osteoclast differentiation will be monitored by localizing and quantitating the emergence of osteoclast specific proteins employing osteoclast specific monoclonal antibodies. We will further determine if osteoclast products in turn effect osteoclast differentiation or expression. We will accomplish this by identifying cellular and matrix factors responsible for osteoclast and osteoblast interactions. It is our aim to determine if local matrix, diffusable cell products, or cell contact are required for skeletal remodelling. Such studies will also contribute to our understanding of normal and inflammatory bone loss and aid in devising therapies for periodontal disease and diabetes associated osteopenia.

National Institute of Health (NIH)
National Institute of Dental & Craniofacial Research (NIDCR)
Research Project (R01)
Project #
Application #
Study Section
Orthopedics and Musculoskeletal Study Section (ORTH)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Washington University
Schools of Arts and Sciences
Saint Louis
United States
Zip Code
Wright, Lorinda M; Maloney, William; Yu, Xuefeng et al. (2005) Stromal cell-derived factor-1 binding to its chemokine receptor CXCR4 on precursor cells promotes the chemotactic recruitment, development and survival of human osteoclasts. Bone 36:840-53
Yu, Xuefeng; Huang, Yuefang; Collin-Osdoby, Patricia et al. (2004) CCR1 chemokines promote the chemotactic recruitment, RANKL development, and motility of osteoclasts and are induced by inflammatory cytokines in osteoblasts. J Bone Miner Res 19:2065-77
Yu, Xuefeng; Collin-Osdoby, Patricia; Osdoby, Philip (2003) SDF-1 increases recruitment of osteoclast precursors by upregulation of matrix metalloproteinase-9 activity. Connect Tissue Res 44 Suppl 1:79-84
Yu, Xuefeng; Huang, Yuefang; Collin-Osdoby, Patricia et al. (2003) Stromal cell-derived factor-1 (SDF-1) recruits osteoclast precursors by inducing chemotaxis, matrix metalloproteinase-9 (MMP-9) activity, and collagen transmigration. J Bone Miner Res 18:1404-18
Rothe, L; Collin-Osdoby, P; Chen, Y et al. (1998) Human osteoclasts and osteoclast-like cells synthesize and release high basal and inflammatory stimulated levels of the potent chemokine interleukin-8. Endocrinology 139:4353-63
Khalkhali-Ellis, Z; Collin-Osdoby, P; Li, L et al. (1997) A human homolog of the 150 kD avian osteoclast membrane antigen related to superoxide dismutase and essential for bone resorption is induced by developmental agents and opposed by estrogen in FLG 29.1 cells. Calcif Tissue Int 60:187-93
Somerman, M J; Berry, J E; Khalkhali-Ellis, Z et al. (1995) Enhanced expression of alpha v integrin subunit and osteopontin during differentiation of HL-60 cells along the monocytic pathway. Exp Cell Res 216:335-41
Collin-Osdoby, P; Oursler, M J; Rothe, L et al. (1995) Osteoclast 121F antigen expression during osteoblast conditioned medium induction of osteoclast-like cells in vitro: relationship to calcitonin responsiveness, tartrate resistant acid phosphatase levels, and bone resorptive activity. J Bone Miner Res 10:45-58
Khalkhali-Ellis, Z (1995) An improved SDS-polyacrylamide gel electrophoresis for resolution of peptides in the range of 3.5-200kDa. Prep Biochem 25:1-9
Groessner-Schreiber, B; Krukowski, M; Lyons, C et al. (1992) Osteoclast recruitment in response to human bone matrix is age related. Mech Ageing Dev 62:143-54

Showing the most recent 10 out of 17 publications