Norepinephrine Inhibition of Mesenchymal Stem Cell and Chondrogenic Progenitor Cell Chondrogenesis and Acceleration of Chondrogenic Hypertrophy
Norepinephrine Inhibition of Mesenchymal Stem Cell and Chondrogenic Progenitor Cell Chondrogenesis and Acceleration of Chondrogenic Hypertrophy
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DOI：
10.1002/art.38695
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发表时间：
2014-09-01
影响因子：
13.3
通讯作者：
Straub, Rainer H.
中科院分区：
文献类型：
--
作者：
Jenei-Lanzl, Zsuzsa Z;Graessel, Susanne;Straub, Rainer H.
客观的。间充质祖细胞软骨形成是软骨生成或再生的生物平台，但交感神经系统对此过程的外部影响尚不清楚。交感神经纤维存在于关节组织中，并且交感神经系统通过例如增加破骨细胞生成来影响肌肉骨骼系统。本研究旨在探讨交感神经递质去甲肾上腺素（NE）在间充质干细胞（MSC）依赖性和软骨祖细胞（CPC）依赖性软骨形成中的作用。方法。使用人 MSC 或 CPC，在 NE、特异性 β-肾上腺素能受体 (β-AR) 激动剂异丙肾上腺素和特异性 β-AR 拮抗剂纳多洛尔的存在下诱导软骨分化。我们研究了交感神经纤维、酪氨酸羟化酶 (TH) 表达、儿茶酚胺生物合成和人体关节滑液水平，以及分化过程中软骨特异性基质沉积。结果。 TH+交感神经纤维存在于滑膜组织、半月板和软骨下骨髓中。此外，膝关节外伤患者的滑液中也显示出高浓度的 NE。在 MSC 或 CPC 软骨形成过程中，β-AR 被表达。用 NE 或异丙肾上腺素处理的软骨聚集体合成了较低量的 II 型胶原和糖胺聚糖。 NE 和异丙肾上腺素治疗剂量依赖性地增加软骨肥大标记物（X 型胶原和基质金属蛋白酶 13）的水平。纳多洛尔逆转了软骨形成的抑制和软骨肥大的上调。结论。我们的研究结果表明，NE 依赖性软骨形成抑制和肥大分化加速。通过抑制软骨修复，这些交感神经的影响在关节创伤后可能很重要。这些发现可能是新的神经软骨形成治疗方案的基础。
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 beta-adrenergic receptor (beta-AR) agonist iso-proterenol, and the specific beta-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, beta-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.