Steven B Abramson, MD

STEVEN B. ABRAMSONProfessor of Medicine and Pathology;
Sr. Vice President and Vice Dean for Education,
Faculty and Academic Affairs
Director, Division of Rheumatology
M.D. 1974 Harvard Medical School

NYU School of Medicine
550 First Avenue
New York, NY 10016
Tel: (212) 263-8003
Fax: (212) 263-3297

Lab Website:
Research Theme(s): Cartilage Biology
Keywords: Chondrocytes, Osteoarthritis, Mesenchymal, Stem Cells

Research Summary:

In OA chondrocytes undergo a series of complex changes that are thought to drive the disease process; these include cellular hypertrophy, increased proliferation, catabolic activation and ultimately, cell death. The regulation of these pathological changes at different stages of disease is under intensive study, with focus on the biomechanical and biochemical signals that regulate each of these discrete chondrocyte responses.

In an effort to identify the underlying cellular changes that are responsible for OA development, we have studied global changes in gene expression in normal and arthritic tissues using microarray and bioinformatics tools. Using this technology we have identified genes and gene families that are either switched on or shut off in osteoarthritis. This work has led to the identification of a number of proteins including cytokines, growth factors and extracellular matrix proteins and regulatory RNA molecules (micro RNAs) important for chondrocyte function. Using animal and in vitro cell and tissue culture models we are investigating their role in chondrocyte (cartilage) homeostasis, development and disease.


From our microarray gene profiling studies, we identified a novel extra cellular matrix protein, F-spondin, in arthritic cartilage. We found that F-spondin, a member of the thrombospondin family of proteins, is significantly increased in osteoarthritic cartilage as well as in rodent models of OA (Figure 4). Further studies from our laboratory indicate that F-spondin has significant effects on human chondrocyte metabolism and skeletal development where it acts to regulate mineralization of cartilage during and long bone formation (endochondral ossification). Ongoing projects are investigating the effects of F-spondin gene knockout on bone and cartilage development, and progression of osteoarthritis in a surgically induced rodent model. We are also investigating the mechanism of F-spondin mediated activation of TGF-b – a pleiotropic growth factor that regulates inflammation and wound repair in a variety of connective tissues. Understanding the regulation of chondrocyte functions by F-spondin could lead to novel strategies for cartilage repair and disease modifying treatments for osteoarthritis.

Inflammatory Mediators:

Understanding the role of inflammatory mediators in the pathogenesis of cartilage degeneration in osteoarthritis (OA) is increasingly recognized as a strategy for the development of mechanism-based therapeutics aimed to slow disease progression. While the catabolic effects of interleukin-1beta, tumor necrosis factor-alpha and nitric oxide are well described, the consequences of the excess production of eicosanoids, (are family of lipids) in the progressive osteoarthritis, are poorly understood. This lack of clarity is, in part, because diverse eicosanoid end-products (Figure 5), are poorly characterized in OA, act via distinct surface receptors, intracellular signaling pathways, and transcription factors to exert highly dissimilar effects on cellular functions. We performed comprehensive determination of the predominant eicosanoids produced by OA chondrocytes in order to clarify the effects of specific end-products on selected gene expression and cartilage homeostasis. Using enzyme immunoassay and LC/MS-MS, we characterized the profile and enzymatic source of the eicosanoids produced by OA cartilage. Based upon our preliminary Studies, we focused on the regulation and action of PGE2. Following the identification of OA predominant eicosanoids, we assessed their effects on differential gene expression of OA and normal chondrocytes. Currently, we are determining the effects of PGE2 and other OA predominant eicosanoids on chondrocyte metabolism (proteoglycan synthesis and degradation), inflammatory mediator production and apoptosis. These studies will provide new insights into the role of eicosanoids in osteoarthritis and elucidate the potential consequences of chronic pharmacologic COX-2 inhibition on the structural integrity of articular cartilage.

Our laboratory is also interested in the differentiation of mesenchymal stem cells into cartilage and bone. Many approaches have met with some success in programming chondrocytes to regenerate cartilage tissue in vitro for subsequent transplantation into diseased joints. However, it has been difficult to generate sufficient numbers of cartilage-producing chondrocytes capable of synthesizing stable, functional articular cartilage. Obtaining chondrocytes from donor tissue is also problematic. Chondrocytes are in very limited supply in the body, and their harvest would require an additional surgical procedure prior to transplantation. The use of mesenchymal stem cells (MSCs) can potentially overcome these limitations. In work that represents a collaboration among our lab (Drs. Attur and Palmer) and Dr. Hernando-Monge , we have recently begun to investigate the role of micro RNAs (miRNAs) in chondrocyte differentiation. These non-coding RNA molecules act by targeting multiple genes to regulate fundamental cellular pathways controlling cell identity and fate. Using gene expression profiling, we have examined miRNA signatures following stimulation of MSCs to cartilage and bone. In each case we have identified several candidate miRNAs that are specifically associated with chondrocyte (cartilage) and osteoblast (bone) formation. Work is underway to determine if these miRNAs can improve cartilage and bone formation and whether they can be exploited to uncover novel pathways that control cell fate determination in MSCs. These studies should aid tissue regeneration strategies by enabling controlled differentiation of stem cells into the desired cell type, so that the transplanted cells can form a functional and durable repair tissue.

Selected publications:


  • Effects of NSAIDs and the Cyclooxygenase-Inhibiting Nitric Oxide Donator (CINOD) NCX 429 on human chondrocytes and cartilage from OA patients [Abstract].  Bolla M.; Viappiani S.; Dave M.; Patel J.; Abramson S.B.; Attur M. Arthritis & rheumatism. 2010; 62: 1477. 
  • miR-7 and miR-130b are differentially regulated during Mesenchymal Stem Cell commitment [Abstract].  Palmer G.; Danielson L.S.; Attur M.; Abramson S.B.; Hernando E.  Arthritis & rheumatism. 2010; 62: 1490 
  • mir-7 and mir-130b are differentially regulated during mesenchymal stem cell commitment [Abstract].  Palmer, G.; Danielson, L.; Attur, M.; Abramson, S. B.; Hernando, E.. Osteoarthritis & cartilage. 2010; 18: S39