Mary Goldring, PhD

Appointments

 

Senior Scientist, Hospital for Special Surgery

 

Selected Publications

 

Tan L, Peng H, Osaki M, Choy BK, Auron PE, Sandell LJ, Goldring MB. (2003) Egr-1 mediates transcriptional repression of COL2A1 promoter activity by interleukin-1b. J. Biol. Chem., 278:17688-17700.

Osaki M, Tan L, Choy BK, Yoshida Y, Cheah KS, Auron PE, Goldring MB. (2003) The TATA-containing core promoter of the type II collagen gene (COL2A1) is the target of interferon-g-mediated inhibition in human chondrocytes: requirement for Stat1a, Jak1 and Jak2. Biochem. J., 369:103-115.

Xu L, Peng H, Wu D, Hu K, Goldring MB, Olsen BR, Li Y. (2005) Activation of the discoidin domain receptor 2 induces expression of matrix metalloproteinase 13 associated with osteoarthritis in mice. J. Biol. Chem., 280:548-555.

Grall FT, Prall WC, Wei W, Gu X, Cho J-Y, Choy BK, Zerbini LF, Inan NS, Goldring SR, Gravallese EM, Goldring MB, Oettgen P, Libermann TA. (2005) The Ets transcription factor ESE-1 mediates induction of the COX-2 gene by LPS in monocytes. Eur. J. Biochem., 272:1676-1687.

Ijiri K, Zerbini LF, Peng H, Correa RG, Lu B, Walsh N, Zhao Y, Taniguchi N, Huang XL, Otu H, Wang H, Wang JF, Komiya S, Ducy P, Rahman MU, Flavell RA, Gravallese E, Oettgen P, Libermann TA, Goldring MB. (2005) A novel role for GADD45b as a mediator of MMP-13 gene expression during chondrocyte terminal differentiation. J. Biol. Chem., 280:38544-38555.

Goldring MB, Tsuchimochi K, Ijiri K. The control of chondrogenesis. (2006) J. Cell. Biochem., 97:33-44.

Goldring MB. (2006) Are bone morphogenetic proteins effective inducers of cartilage repair? Ex vivo transduction of muscle-derived stem cells [Editorial]. Arthritis Rheum., 54:387-389.

Goldring, MB (2006) Update on the biology of the chondrocyte and new approaches to treating cartilage diseases. Best Pract. Res. Clin. Rheumatol., 20:1003-25.

For more publications, please see the PubMed listing.  

Research Description

Laboratory of Cartilage Biology

Research in the laboratory is focused on defining the molecular and cellular mechanisms that lead to alterations in remodeling of cartilage in osteoarthritis and inflammatory joint diseases. Proteins produced in response to excessive mechanical loading and inflammation in joints not only stimulate the production of enzymes that break down the cartilage but also impair the ability of the chondrocyte, the unique cell type in adult cartilage, to repair the damage.To study the regulation of gene expression by inflammatory and destructive cytokines, such as interleukin-1 (IL-1) and tumor necrosis factor-a (TNF-a), cell culture models of primary chondrocytes isolated from cartilage retrieved from patients undergoing joint surgery and human chondrocyte cell lines developed in this laboratory are used to analyze the signaling pathways and transcription factors that target type II collagen (COL2A1), matrix metalloproteinase-13 (MMP-13) and other chondrocyte genes. This work has defined novel roles for transcription factors, including IL-1-induced Egr-1 and ESE-1 and interferon-g-induced Stat1, in the suppression of COL2A1 transcription. ESE-1, which is epithelial cell-specific in normal physiological conditions, but is induced by inflammatory and destructive cytokines in chondrocytes and other non-epithelial cell types and mediates the induction of destructive proteinases and inflammatory mediators. Current work focuses on mechanisms by which ESE-1 suppresses COL2A1 and upregulates MMP-13.

Recent work has uncovered new roles of genes, which were not known previously to act in cartilage, in the regulation of chondrocyte differentiation during development and in dysregulated chondrocyte function in osteoarthritis. Genes regulated by bone morphogenetic proteins (BMPs), which regulate chondrocyte differentiation in development and influence articular cartilage repair, have been detected by DNA microarray analysis.One of these genes, growth arrest and DNA damage (GADD)-45b also increases MMP-13 gene expression. Both GADD45b and ESE-1 are upregulated in mouse models of osteoarthritis due to deficient expression of cartilage-specific collagen genes and in human osteoarthritic cartilage. Current studies involve both in vitro analysis of signaling and transcriptional mechanisms that regulate the expression and activities of GADD45b and ESE-1 and in vivo analysis of the consequences of knockout and transgenic overexpression of these genes in mouse models of defective skeletal development and osteoarthritis. Since degradation and defective repair of cartilage matrix are major features accounting for the loss of function of articular cartilage in osteoarthritis, these studies are expected to lead to an understanding of the critical signals involved and to the development of targeted therapies that both block cartilage damage and promote effective cartilage repair.