Abstract
Osteoarthritis (OA) is a degenerative joint disease that not only causes cartilage loss but also structural damage in all joint tissues. Joints are innervated by alpha-calcitonin gene-related peptide (αCGRP) and substance P (SP)-positive sensory nerve fibers. Alteration of sensory joint innervation could be partly responsible for degenerative changes in joints that contribute to the development of OA. Therefore, our aim was to analyze and compare the molecular effects of SP and αCGRP on the metabolism of articular chondrocytes from OA patients and non-OA cartilage donors. We treated the cells with SP or αCGRP and analysed the influence of these neuropeptides on chondrocyte metabolism and modulation of signaling pathways. In chondrocytes from healthy cartilage, SP had minimal effects compared with its effects on OA chondrocytes, where it induced inflammatory mediators, inhibited chondrogenic markers and promoted apoptosis and senescence. Treatment with αCGRP also increased apoptosis and senescence and reduced chondrogenic marker expression in OA chondrocytes, but stimulated an anabolic and protective response in healthy chondrocytes. The catabolic influence of SP and αCGRP might be due to activation of ERK signaling that could be counteracted by an increased cAMP response. We suggest that a switch between the G-subunits of the corresponding receptors after binding their ligands SP or αCGRP plays a central role in mediating the observed effects of sensory neuropeptides on chondrocytes.
Highlights
Osteoarthritis (OA) is the world’s most common musculoskeletal disorder, research efforts have not yet been able to define its exact etiology [1, 2]
Whereas for substance P (SP) no differences were found between both groups (OA-CH: 22,91 ± 4,762 pg/ml vs. non-OA-CH: 24,85 ± 3,218 pg/ml) (Figure 1A), the level of alpha-calcitonin gene-related peptide (aCGRP) was increased by trend in the supernatant of OA-CH (191,3 ± 93,77 pg/ml) compared to non-OA-CH (88,79 ± 36,00 pg/ml), not statistically significantly (Figure 1B)
We suggest that there is a pro-inflammatory and destructive effect through active ERK signaling induced by SP and aCGRP in both healthy and OA articular chondrocytes
Summary
Osteoarthritis (OA) is the world’s most common musculoskeletal disorder, research efforts have not yet been able to define its exact etiology [1, 2]. SWI/SNF Mutations as Potential Biomarkers (SP) and alpha-calcitonin gene-related peptide (aCGRP), innervate synovium, trabecular and subchondral bone, bone marrow, periosteum and fracture callus. In addition to their classical neurological features, trophic effects that are critical for joint tissue and bone homeostasis under physiological and pathophysiological conditions have been noted [3, 4]. Suri et al have localized SP- and aCGRP-positive nerve fibers in the articular cartilage of OA patients They hypothesize that during the pathogenesis of OA, fine unmyelinated nerves grow into joint structures through vascular channels, mainly from subchondral bone breaching through the tidemark rather than coming from synovium or periosteum [8]. Our data will contribute to a better understanding of potential new application routes using these neuropeptides or their inhibitors to extend and improve the therapy spectrum for OA patients
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
