Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.
Norepinephrine (NE) Affects Mesenchymal Stem Cell (MSCs) Chondrogenesis and Accordingly the Self-Regeneration Capacity of Cartilage.
Jenei-Lanzl1, Zsuzsa, Angele2, Peter, Straub3, Rainer H.
Laboratory of Experimental Rheumatology and Neuroendocrine Immunology, Department of Internal Medicine, University Hospital Regensburg, Regensburg, Germany
Department of Trauma Surgery, University Hospital Regensburg, Germany, Regensburg, Germany
University Hospital Regensburg, Regensburg, Germany
It is known that sympathetic nerve fibers are present in healthy and osteoarthritic (OA) synovium and that the sympathetic nervous system mediates numerous effects on adult skeletal system. The presence of mesenchymal stem cells (MSCs) in healthy or arthritic cartilage has also been confirmed. In addition, MSCs migrating from synovium into the cartilage and differentiating into chondrocytes has been described. This might be the reason for increased MSC number in OA. The aim of this study was to investigate the effects of the most important sympathetic neurotransmitter norepinephrine (NE) on MSC chondrogenesis.
Human bone marrow derived MSCs were expanded in serum containing medium. After achieving confluence, 3D aggregates were formed and chondrogenesis was initiated by the use of a specific serum-free chondrogenic medium. Parallel to control conditions, aggregates were incubated with different concentrations of NE (10-9 to 10-6 M). Based on the first results aggregates were treated with specific b-adrenoceptor agonist (isoproterenol) or antagonist (nadolol). After 21 days, the quality of aggregate chondrogenesis was evaluated macroscopically, histologically and biochemically. Furthermore, specific adrenoceptors (a1 and b2) were detected.
Aggregates treated with high NE concentrations (10-7 to 10-6M) or with isoproterenol were smaller, showed a weaker staining of cartilaginous matrix and significantly reduced type II collagen synthesis than control aggregates or aggregates treated with lower NE concentrations or nadolol alone. Nadolol reversed the effects of NE and isoproterenol. In addition, acceleration of chondrocyte hypertrophy (increased MMP13 and type X collagen expression) was observed after NE and isoproterenol addition, which was reversed by nadolol. Presence of specific adrenoceptors (a1 and b2) was shown in the aggregates undergoing chondrogenesis.
The suppression of chondrogenesis by high NE or isoproterenol suggests that the b-adrenoceptors mediate this effect. This pathway might influence existing or migrating MSCs and play a role in OA development and manifestation. Further experiments are required to discover underlying signalling pathways, which might help to develop therapy options for the regeneration of injured or osteoarthritic cartilage tissue.
To cite this abstract, please use the following information:
Jenei-Lanzl, Zsuzsa, Angele, Peter, Straub, Rainer H.; Norepinephrine (NE) Affects Mesenchymal Stem Cell (MSCs) Chondrogenesis and Accordingly the Self-Regeneration Capacity of Cartilage. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :1775