Richard L. Menschel Research Chair, Hospital for Special Surgery
Professor of Medicine, Weill Cornell Medical College
Steven R.Goldring, M.D., chief scientific officer at HSS, received the Paul Klemperer Award and Medal for outstanding achievements and contributions to the study of connective tissues and their disease by the Arthritis Foundation New York Chapter and presented the 21st Paul Klemperer Lecture “Mechanisms of Pathologic Bone Remodeling Pathology Teaches Physiology” at The New York Academy of Medicine, Nov. 11.
Dr. Goldring joined HSS in July 2006. From 1996 to July 2006, he was a Professor of Medicine at Harvard Medical School and chief of rheumatology at Beth Israel Deaconess Medical Center. He has also served as the director of the New England Baptist Bone and Joint Institute, in collaboration with the Beth Israel Deaconess Medical Center since its establishment in 1996. Dr. Goldring has served as a consultant or Principal Investigator in National Institutes of Health sponsored research programs and in the pharmaceutical industry, and as a consultant to numerous biotechnology and pharmaceutical companies. He received his medical training at Peter Bent Brigham Hospital and the Massachusetts General Hospital. He is the author of numerous scientific publications. Dr. Goldring holds a medical degree from Washington University School of Medicine.
Dacquin R, Davey RA, Laplace C, Levasseur R, Morris HA, Goldring SR, Gebre-Medhin S, Galson DL, Zajac JD, Karsenty G. Amylin inhibits bone resorption while the calcitonin receptor controls bone formation in vivo. J Cell Biol. 2004; 164:509-14.
Brown C, Gaspar J, Pettit A, Lee R, Gu X, Wang H, Manning C, Voland C, Goldring SR, Goldring MB, Libermann TA, Gravalllese EM, Oettgen P. ESE-1 is a novel transcriptional mediator of angiopoietin-1 expression in the setting of inflammation. J Biol Chem. 2004; 164(4):509-14.
Garrigues GE, Cho DR, Rubash HE, Goldring SR, Herndon JH, Shanbhag AS. Gene expression clustering using self-organizing maps: analysis of the macrophage response to particulate biomaterials. Biomaterials. 2005; 26(16):2933-45.
Shen Z, Crotti TN, McHugh KP, Matsuzaki K, Gravallese EM, Bierbaum BE, Goldring SR. The role played by cell-substrate interactions in the pathogenesis of osteoclast-mediated peri-implant osteolysis. Arthritis Res Ther. 2006; 8(3):R70 [Epub ahead of print].
Crotti TN, Flannery M, Walsh NC, Fleming JD, Goldring SR, McHugh KP. NFATc1 regulation of the human beta(3) integrin promoter in osteoclast differentiation. Gene. 2006; 372:92-102. Epub 2006 Mar 2.For more publications, please see the PubMed listing.
The skeleton provides essential functions that include mechanical support, protection of vital organs and maintenance of calcium and mineral ion homeostasis. A network of endocrine and local bone-specific molecules maintain skeletal integrity and control metabolic activities through a highly regulated system of cellular remodeling that involves cells that resorb (osteoclasts) and rebuild (osteoblasts) the mineralized matrix of skeletal tissues. In disorders such as osteoporosis, malignancies that target the skeleton and in inflammatory conditions such as rheumatoid and related forms of arthritis, there is a disturbance in the equilibrium between bone-forming and resorbing cells that leads progressive focal or systemic bone loss and to potential disturbance in blood calcium and mineral levels.
My laboratory has focused on dissecting the cellular and molecular mechanisms involved in the regulation of physiological and pathological bone remodeling. The ultimate goal of these studies has been to develop more effective and direct therapeutic strategies for blocking bone loss in disorders such as osteoporosis, inflammatory arthritis and malignancies.
In the early 1990s, the laboratory successfully cloned the human calcitonin receptor. Expression of this receptor definitively identifies the osteoclast, which is the principal cell type responsible for bone resorption. More recently, the osteoclast-specific promoter of the calcitonin receptor has been cloned and this has permitted direct examination of the mechanisms regulating osteoclast differentiation and activation at a molecular level. Reagents and molecular approaches derived from these studies have been used to study several human models of pathological bone loss, including rheumatoid arthritis and malignancies that affect the skeleton. These studies have been extended to include the investigation of the role of cell-matrix interactions and the effects of cytokines and related soluble mediators of inflammation on osteoclast-mediated bone resorption in physiologic bone remodeling and in inflammatory arthritis and malignancies. In addition, investigations have included the evaluation of the effects of orthopaedic implant biomaterials used for total joint replacement and/or bone augmentation or substitution. Research has been directed at characterization of the molecular mechanisms and cell-associated signaling pathways by which foreign implant biomaterials modulate cell and tissue responses. This information is of critical importance for the development of more effective strategies for treating end-stage destructive arthritis and for creating improved approaches for preventing aseptic loosening after total joint replacement.