Bone marrow contains a class of progenitor cells, termed Mesenchymal Stem Cells, which can differentiate into osteoblasts and chondrocytes: these stem cells are distinct from hematopoietic stem cells. Previous studies have shown that Mesenchymal Stem Cells can be isolated from the marrow of a variety of animals and mitotically expanded many-fold in culture. Culture-expanded cells have been implanted into immunocompatible host animals, in diffusion chambers or ceramic cubes where they differentiate into cartilage and bone, depending on the assay conditions. In addition, culture-expanded Mesenchymal Stem Cells from rabbit marrow have recently been used to regenerate cartilage in full-thickness articular cartilage defects in the rabbit knee. Methods have also been developed in our laboratory to culture expand Mesenchymal Stem Cells from human marrow. Until recently, there were no known phenotypic markers (i.e. morphology, enzyme staining or extracellular matrix or cell surface proteins) unique to Mesenchymal Stem Cells. As a first step to identifying such markers, we generated three monoclonal antibodies, SH2, SH3, and SH4 that selectively stain cell surface antigens on culture-expanded human marrow-derived Mesenchymal Stem Cells. In this study, we propose to identify the cell surface antigens recognized by the SH2, SH3, and SH4 monoclonal antibodies by liberating, purifying and biochemically characterizing, including partial amino acid sequencing, the SH2, SH3, and SH4 antigens. The partial amino acid sequences will be compared to known amino acid sequence databases to determine if the SH-antigens are known or previously uncharacterized proteins. Experimentation will then be developed to identify and sequence the genes encoding these proteins. In addition, binding assays will be used to investigate possible functional roles of the SH-antigens on the surface of Mesenchymal Stem Cells. The data generated from these studies should add to our ability to manipulate and monitor Mesenchymal Stem Cells and learn more about the role these cells have in cartilage tissue development and repair.

Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Case Western Reserve University
United States
Zip Code
Miwa, Hazuki E; Gerken, Thomas A; Huynh, Tru D et al. (2009) Conserved sequence in the aggrecan interglobular domain modulates cleavage by ADAMTS-4 and ADAMTS-5. Biochim Biophys Acta 1790:161-72
Atif, U; Philip, A; Aponte, J et al. (2008) Absence of association of asporin polymorphisms and osteoarthritis susceptibility in US Caucasians. Osteoarthritis Cartilage 16:1174-7
Kraus, V B; Jordan, J M; Doherty, M et al. (2007) The Genetics of Generalized Osteoarthritis (GOGO) study: study design and evaluation of osteoarthritis phenotypes. Osteoarthritis Cartilage 15:120-7
Miwa, Hazuki E; Gerken, Thomas A; Huynh, Tru D et al. (2006) Mammalian expression of full-length bovine aggrecan and link protein: formation of recombinant proteoglycan aggregates and analysis of proteolytic cleavage by ADAMTS-4 and MMP-13. Biochim Biophys Acta 1760:472-86
Holderbaum, D; Malvitz, T; Ciesielski, C J et al. (2005) A newly described hereditary cartilage debonding syndrome. Arthritis Rheum 52:3300-4
Denko, Charles W; Malemud, Charles J (2005) Role of the growth hormone/insulin-like growth factor-1 paracrine axis in rheumatic diseases. Semin Arthritis Rheum 35:24-34
Ievers-Landis, Carolyn E; Burant, Christopher; Drotar, Dennis et al. (2005) A randomized controlled trial for the primary prevention of osteoporosis among preadolescent girl scouts: 1-year outcomes of a behavioral program. J Pediatr Psychol 30:155-65
Vashishth, D (2005) Collagen glycation and its role in fracture properties of bone. J Musculoskelet Neuronal Interact 5:316
Denko, Charles W; Malemud, Charles J (2005) Serum growth hormone and insulin but not insulin-like growth factor-1 levels are elevated in patients with fibromyalgia syndrome. Rheumatol Int 25:146-51
Denko, Charles W; Malemud, Charles J (2004) Age-related changes in serum growth hormone, insulin-like growth factor-1 and somatostatin in system lupus erythematosus. BMC Musculoskelet Disord 5:37

Showing the most recent 10 out of 92 publications