Sympathetic Neurotransmitters Modulate Osteoclastogenesis and Osteoclast Activity in the Context of Collagen-Induced Arthritis

被引：15

作者：

Muschter, Dominique ^{[1
,3
]}

Schaefer, Nicole ^{[1
]}

Stangl, Hubert ^{[2
]}

Straub, Rainer H. ^{[2
]}

Graessel, Susanne ^{[1
,3
]}

机构：

[1] Univ Hosp Regensburg, Dept Orthoped Surg Expt Orthoped, Regensburg, Bavaria, Germany

[2] Univ Hosp Regensburg, Lab Expt Rheumatol & Neuroendocrine Immunol, Dept Internal Med 1, Regensburg, Bavaria, Germany

[3] BioPark I, Ctr Med Biotechnol, Regensburg, Bavaria, Germany

来源：

PLOS ONE | 2015年 / 10卷 / 10期

关键词：

VASOACTIVE-INTESTINAL-PEPTIDE; RHEUMATOID-ARTHRITIS; INFLAMMATORY ARTHRITIS; ADENYLATE-CYCLASE; BONE-RESORPTION; NERVOUS-SYSTEM; CATHEPSIN-K; CELLS; MICE; OSTEOPROTEGERIN;

D O I：

10.1371/journal.pone.0139726

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Excessive synovial osteoclastogenesis is a hallmark of rheumatoid arthritis (RA). Concomitantly, local synovial changes comprise neuronal components of the peripheral sympathetic nervous system. Here, we wanted to analyze if collagen-induced arthritis (CIA) alters bone marrow-derived macrophage (BMM) osteoclastogenesis and osteoclast activity, and how sympathetic neurotransmitters participate in this process. Therefore, BMMs from Dark Agouti rats at different CIA stages were differentiated into osteoclasts in vitro and osteoclast number, cathepsin K activity, matrix resorption and apoptosis were analyzed in the presence of acetylcholine (ACh), noradrenaline (NA) vasoactive intestinal peptide (VIP) and assay-dependent, adenylyl cyclase activator NKH477. We observed modulation of neurotransmitter receptor mRNA expression in CIA osteoclasts without affecting protein level. CIA stage-dependently altered marker gene expression associated with osteoclast differentiation and activity without affecting osteoclast number or activity. Neurotransmitter stimulation modulated osteoclast differentiation, apoptosis and activity. VIP, NA and adenylyl cyclase activator NKH477 inhibited cathepsin K activity and osteoclastogenesis (NKH477, 10-6M NA) whereas ACh mostly acted pro-osteoclastogenic. We conclude that CIA alone does not affect metabolism of in vitro generated osteoclasts whereas stimulation with NA, VIP plus specific activation of adenylyl cyclase induced anti-resorptive effects probably mediated via cAMP signaling. Contrary, we suggest pro-osteoclastogenic and pro-resorptive properties of ACh mediated via muscarinic receptors.

引用

页数：21

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