{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T23:26:37Z","timestamp":1787613997472,"version":"build-2736575974"},"reference-count":47,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2014,8,26]],"date-time":"2014-08-26T00:00:00Z","timestamp":1409011200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["AN 309\/1-1 and CA 933\/1-1"],"award-info":[{"award-number":["AN 309\/1-1 and CA 933\/1-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2014,9]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Mesenchymal progenitor cell chondrogenesis is the biologic platform for the generation or regeneration of cartilage, but the external influence of the sympathetic nervous system on this process is not yet known. Sympathetic nerve fibers are present in articular tissue, and the sympathetic nervous system influences the musculoskeletal system by, for example, increasing osteoclastogenesis. This study was initiated to explore the role of the sympathetic neurotransmitter norepinephrine (NE) in mesenchymal stem cell (MSC)\u2013dependent and cartilage progenitor cell (CPC)\u2013dependent chondrogenesis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Using human MSCs or CPCs, chondrogenic differentiation was induced in the presence of NE, the specific \u03b2\u2010adrenergic receptor (\u03b2\u2010AR) agonist isoproterenol, and the specific \u03b2\u2010AR antagonist nadolol. We studied sympathetic nerve fibers, tyrosine hydroxylase (TH) expression, catecholamine biosynthesis, and synovial fluid levels in human joints, as well as cartilage\u2010specific matrix deposition during differentiation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>TH+ sympathetic nerve fibers were present in the synovial tissue, meniscus, and subchondral bone marrow. In addition, synovial fluid from patients with knee trauma demonstrated high concentrations of NE. During MSC or CPC chondrogenesis, \u03b2\u2010AR were expressed. Chondrogenic aggregates treated with NE or isoproterenol synthesized lower amounts of type II collagen and glycosaminoglycans. NE and isoproterenol treatment dose\u2010dependently increased the levels of cartilage hypertrophy markers (type X collagen and matrix metalloproteinase 13). Nadolol reversed the inhibition of chondrogenesis and the up\u2010regulation of cartilage hypertrophy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings demonstrate NE\u2010dependent inhibition of chondrogenesis and acceleration of hypertrophic differentiation. By inhibiting cartilage repair, these sympathetic influences can be important after joint trauma. These findings may be a basis for novel neurochondrogenic therapeutic options.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.38695","type":"journal-article","created":{"date-parts":[[2014,5,12]],"date-time":"2014-05-12T13:50:55Z","timestamp":1399902655000},"page":"2472-2481","source":"Crossref","is-referenced-by-count":45,"title":["Norepinephrine Inhibition of Mesenchymal Stem Cell and Chondrogenic Progenitor Cell Chondrogenesis and Acceleration of Chondrogenic Hypertrophy"],"prefix":"10.1002","volume":"66","author":[{"given":"Zsuzsa","family":"Jenei\u2010Lanzl","sequence":"first","affiliation":[{"name":"University Hospital Regensburg Regensburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Gr\u00e4ssel","sequence":"additional","affiliation":[{"name":"University Hospital Regensburg Regensburg 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