Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose:
The high potential of mesenchymal stem cells (MSCs) in cartilage regeneration is undoubtful. The presence of 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, which might be the reason for increased MSC number in OA. Furthermore, 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. Therefore, the aim of this study was to investigate the effects of the most important sympathetic neurotransmitter norepinephrine (NE) on MSC chondrogenesis.
Methods:
To find possible natural sources of local catecholamines in human joint material, we studied sympathetic nerve fibers (tyrosine hydroxylase (TH) expression), catecholamine biosynthesis and synovial fluid levels. Human bone marrow derived MSCs were expanded and chondrogenesis was initiated in a 3D aggregate culture. Endogenous catecholamine production of hMSCs was analyzed during proliferation and chondrogenesis via HPLC. Parallel to control conditions, aggregates were incubated with different NE concentrations and specific β-adrenoceptor agonist (isoproterenol) or antagonist (nadolol). After 21 days, chondrogenesis quality was evaluated macroscopically, histologically and biochemically. Furthermore, specific adrenoceptors (AR) were detected.
Results:
In the human joint, TH-positive fibers and/or single cells were present in synovial tissue, meniscus, and subchondral bone marrow. In addition, knee-traumatized patients demonstrated high NE concentrations in synovial fluid. At various stages of human MSC chondrogenesis, βAR were expressed. No endogenous catecholamine synthesis was detected during chondrogenesis. Chondrogenic MSC aggregates treated with NE or isoproterenol synthesized lower amounts of type II collagen and glycosaminoglycans. NE and isoproterenol dose-dependently increased markers of cartilage hypertrophy (collagen type X and MMP-13). Nadolol reversed inhibition of chondrogenesis and up-regulation of cartilage hypertrophy.
Conclusion:
The suppression of MSC-dependent chondrogenesis by high NE or isoproterenol suggests that the β-adrenoceptors mediate this effect. By inhibition of cartilage repair, these sympathetic influences can be important after multiple minor and major joint traumata. These findings can be a basis for novel neuro-chondrogenic therapeutic options.
Disclosure:
Z. Jenei-Lanzl,
None;
P. Angele,
None;
F. Kees,
None;
G. Pongratz,
None;
R. H. Straub,
None.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/norepinephrine-ne-inhibits-mesenchymal-stem-cell-mscs-chondrogenesis-by-accelerating-hypertophy-relevance-for-cartilage-regeneration/