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Norepinephrine Inhibition of Mesenchymal Stem Cell and Chondrogenic Progenitor Cell Chondrogenesis and Acceleration of Chondrogenic Hypertrophy
Author(s) -
JeneiLanzl Zsuzsa,
Grässel Susanne,
Pongratz Georg,
Kees Frieder,
Miosge Nicolai,
Angele Peter,
Straub Rainer H.
Publication year - 2014
Publication title -
arthritis and rheumatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.106
H-Index - 314
eISSN - 2326-5205
pISSN - 2326-5191
DOI - 10.1002/art.38695
Subject(s) - chondrogenesis , mesenchymal stem cell , endocrinology , medicine , microbiology and biotechnology , chemistry , progenitor cell , cartilage , stem cell , anatomy , biology
Objective 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)–dependent and cartilage progenitor cell (CPC)–dependent chondrogenesis. Methods Using human MSCs or CPCs, chondrogenic differentiation was induced in the presence of NE, the specific β‐adrenergic receptor (β‐AR) agonist isoproterenol, and the specific β‐AR antagonist nadolol. We studied sympathetic nerve fibers, tyrosine hydroxylase (TH) expression, catecholamine biosynthesis, and synovial fluid levels in human joints, as well as cartilage‐specific matrix deposition during differentiation. Results 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, β‐AR were expressed. Chondrogenic aggregates treated with NE or isoproterenol synthesized lower amounts of type II collagen and glycosaminoglycans. NE and isoproterenol treatment dose‐dependently increased the levels of cartilage hypertrophy markers (type X collagen and matrix metalloproteinase 13). Nadolol reversed the inhibition of chondrogenesis and the up‐regulation of cartilage hypertrophy. Conclusion Our findings demonstrate NE‐dependent 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.