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Arthritis Research and Therapy

, 16:485

At the interface between immunology and neurology in rheumatic diseases

Abstract

The peripheral nervous system is critically involved in bone metabolism, osteogenesis, and bone remodeling.
Nerve fibers of sympathetic and sensory origin innervate synovial tissue and subchondral bone of diathrodial joints.
They modulate vascularization and matrix differentiation during endochondral ossification in embryonic limb development, indicating a distinct role in skeletal growth and limb regeneration processes.
In pathophysiological situations, the innervation pattern of sympathetic and sensory nerve fibers is altered in adult joint tissues and bone.
Various resident cell types of the musculoskeletal system express receptors for sensory and sympathetic neurotransmitters.
Osteoblasts, osteoclasts, mesenchymal stem cells, synovial fibroblasts, and different types of chondrocytes produce distinct subtypes of adrenoceptors, receptors for vasointestinal peptide, for substance P and calcitonin gene-related peptide.
Many of these cells even synthesize neuropeptides such as substance P and calcitonin gene-related peptide and are positive for tyrosine-hydroxylase, the rate-limiting enzyme for biosynthesis of catecholamines.
Sensory and sympathetic neurotransmitters modulate osteo-chondrogenic differentiation of mesenchymal progenitor cells during endochondral ossification in limb development.
In adults, sensory and sympathetic neurotransmitters are critical for bone regeneration after fracture and are involved in the pathology of inflammatory diseases as rheumatoid arthritis which manifests mainly in joints.
Possibly, they might also play a role in pathogenesis of degenerative joint disorders, such as osteoarthritis.
All together, accumulating data imply that sensory and sympathetic neurotransmitters have crucial trophic effects which are critical for proper limb formation during embryonic skeletal growth.
In adults, they modulate bone regeneration, bone remodeling, and articular cartilage homeostasis in addition to their classic neurological actions.

AbbreviationsARadrenoceptor

BMSCbone marrow-derived stem cell

CGRPcalcitonin gene-related peptide

ILinterleukin

MMPmatrix metalloprotease

NEnorepinephrine

NPneuropilin

NPYneuropeptide Y

OAosteoarthritis

OPGosteoprotegerin

Plxplexin

RArheumatoid arthritis

RANKLreceptor activator of nuclear factor kappa-B ligand

Semasemaphorin

SPsubstance P

THtyrosine-hydroxylase

VEGFvascular endothelial growth factor

VIPvasoactive intestinal peptide

Electronic supplementary materialThe online version of this article doi:10.1186-s13075-014-0485-1 contains supplementary material, which is available to authorized users.

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Author: Susanne Grässel

Source: https://link.springer.com/



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