Publications in 2019


 

 

Osteoarthritis Cartilage in press

 

Mechanosensitive MiRs Regulated by Anabolic and Catabolic Loading of Human Cartilage

 

Hecht N, Johnstone B, Angele P, Walker T, Richter W.

(SP3 + SP7)                     

 

Full Text

Journal Link

 

Abstract

Elucidation of whether miRs are involved in mechanotransduction pathways by which cartilage is maintained or disturbed has a particular importance in our understanding of osteoarthritis (OA) pathophysiology. The aim was to investigate whether mechanical loading influences global miR-expression in human chondrocytes and to identify mechanosensitive miRs responding to beneficial and non-beneficial loading regimes as potential to obtain valuable diagnostic or therapeutic targets to advance OA-treatment.

 

PMID: 31009748

DOI: https://doi.org/10.1016/j.joca.2019.04.010

 

 


 

 

Int. J. Mol. Sci. 201920(5), 1212; doi:10.3390/ijms20051212

 

Role of Norepinephrine in IL-1β-Induced Chondrocyte Dedifferentiation under Physioxia

 

Saskia Speichert, Natalie Molotkov, Karima El Bagdadi, Andrea Meurer, Frank Zaucke, Zsuzsa Jenei-Lanzl

(SP8)                     

 

Full Text

https://www.mdpi.com/1422-0067/20/5/1212/htm

 

Abstract

As part of the pathogenesis of osteoarthritis (OA), chondrocytes lose their phenotype and become hypertrophic, or dedifferentiate, mainly driven by interleukin-1β (IL-1β). The contribution of other factors to the dedifferentiation process is not completely understood. Recent studies suggested a dose-dependent role for the sympathetic neurotransmitter norepinephrine (NE) in OA chondrocyte metabolism. Therefore, the aim of this study was to analyze the contribution of NE (10−8 M, 10−6 M) to human articular OA chondrocyte dedifferentiation in the absence or presence of IL-1β (0.5 ng/mL). Here, we demonstrate that OA chondrocytes express α2A-, α2C- and β2-adrenoceptors (AR) and show the characteristic shift towards a fibroblast-like shape at day 7 in physioxic monolayer culture. NE alone did not affect morphology but, in combination with IL-1β, markedly accelerated this shift. Moderate glycosaminoglycan (GAG) staining was observed in untreated and NE-treated cells, while IL-1β strongly decreased GAG deposition. IL-1β alone or in combination with NE decreased SOX9, type II collagen, COMP, and aggrecan, and induced MMP13 and ADAMTS4 gene expression, indicating an accelerated dedifferentiation. NE alone did not influence gene expression and did not modulate IL-1β-mediated effects. In conclusion, these results indicate that low-grade inflammation exerts a dominant effect on chondrocyte dedifferentiation and should be targeted early in OA therapy. 

 

Keywords

osteoarthritis; chondrocytes; dedifferentiation; norepinephrine; interleukin-1β; adrenoceptors; physioxia

 

 


 

 

Int J Mol Sci. 2019 Feb 12;20(3). pii: E770. doi: 10.3390/ijms20030770.

 

Developmental Transformation and Reduction of Connective Cavities within the Subchondral Bone.

 

Shahed Taheri, Thomas Winkler, Lia Sabrina Schenk , Carl Neuerburg,, Sebastian Felix Baumbach, Jozef Zustin, Wolfgang Lehmann, Arndt Friedrich Schilling

(SP5)                     

 

Full Text

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6387253/pdf/ijms-20-00770.pdf

 

Abstract

It is widely accepted that the subchondral bone (SCB) plays a crucial role in the 15 physiopathology of osteoarthritis (OA), although its contribution is still debated. Much of the pre16 clinical research on the role of SCB is concentrated on comparative evaluations of healthy vs. early 17 OA or early OA vs. advanced OA cases, while neglecting how pure maturation could change the 18 SCB’s microstructure. To assess the transformations of the healthy SCB from young age to early 19 adulthood, we examined the microstructure and material composition of the medial condyle of the 20 femur in calves (3 months) and cattle (18 months) for the calcified cartilage (CC) and the 21 subchondral bone plate (SCBP). The entire subchondral zone (SCZ) was significantly thicker in 22 cattle compared to calves, although the proportion of the CC and SCBP thicknesses were relatively 23 constant. The trabecular number (Tb.N.) and the connectivity density (Conn.D) was significantly 24 higher in the deeper region of the SCZ, while the bone volume fraction (BV/TV), and the degree of 25 anisotropy (DA) were more affected by age rather than the region. The mineralization increased 26 within the first 250 µm of the SCZ irrespective of sample type, and became stable thereafter. Cattle 27 exhibited higher mineralization than calves at all depths, with a mean Ca/P ratio of 1.59 and 1.64 for 28 calves and cattle, respectively. Collectively, these results indicate that the SCZ is highly dynamic at 29 early age, and CC is the most dynamic layer of the SCZ.

 

Keywords

Bone histomorphometry; Subchondral bone; Microcomputed tomography; 31 Osteoarthritis; Calcified cartilage

 

 


 

 

Int J Mol Sci. 2019 Feb; 20(3): 503. Published online 2019 Jan 24.

 

Sensory Neuropeptides and their Receptors Participate in Mechano-Regulation of Murine Macrophages

 

Dominique Muschter, Anna-Sophie Beiderbeck, Tanja Späth, Christian Kirschneck, Agnes Schröder and Susanne Grässel

(SP4)                     

 

Full Text

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6386869/pdf/ijms-20-00503.pdf

 

Abstract

This study aimed to analyze if the sensory neuropeptide SP (SP) and the neurokinin receptor 1 (NK1R) are involved in macrophage mechano-transduction, similar to chondrocytes, and if alpha-calcitonin gene-related peptide (αCGRP) and the CGRP receptor (CRLR/Ramp1) show comparable activity. Murine RAW264.7 macrophages were subjected to a cyclic stretch for 1–3 days and 4 h/day. Loading and neuropeptide effects were analyzed for gene and protein expression of neuropeptides and their receptors, adhesion, apoptosis, proliferation and ROS activity. Murine bone marrow-derived macrophages (BMM) were isolated after surgical osteoarthritis (OA) induction and proliferation, apoptosis and osteoclastogenesis were analyzed in response to loading. Loading induced NK1R and CRLR/Ramp1 gene expression and altered protein expression in RAW264.7 macrophages. SP protein and mRNA level decreased after loading whereas αCGRP mRNA expression was stabilized. SP reduced adhesion in loaded RAW264.7 macrophages and both neuropeptides initially increased the ROS activity followed by a time-dependent suppression. OA induction sensitized BMM to caspase 3/7 mediated apoptosis after loading. Both sensory neuropeptides, SP and αCGRP, and their receptors are involved in murine macrophage mechano-transduction affecting neuropeptide impact on adhesion and ROS activity. OA induction altered BMM apoptosis in response to loading indicate that OA-associated biomechanical alterations might affect the macrophage population.

 

Keywords

cyclic stretch, mechan-oregulation, murine macrophages, substance P, alpha-calcitonin gene-related peptide, neurokinin receptor, CGRP receptor, destabilized medial meniscus

 

doi10.3390/ijms20030503

PMCID: PMC6386869

PMID: 30682804

 

 


 

 

Ann Stem Cell Res 2(1): 001-005. 2019 Feb 09.

 

Integrin α10β1-selected Equine MSCs have Improved Chondrogenic Differentiation, Immunomodulatory and Cartilage Adhesion Capacity

 

Kristina Uvebrant, Linda Reimer Rasmusson, Jan F. Talts, Paolo Alberton, Attila Aszodi and Evy Lundgren-Äkerlund

(SP1)                     

 

Full Text

https://www.somatopublications.com/integrin-%CE%B110%CE%B21-selected-equine-mscs-have-improved-chondrogenic-differentiation-immunomodulatory-and-cartilage-adhesion-capacity.pdf


Abstract

Cell therapy based on multipotent, adult mesenchymal stem cells (MSCs) is a promising method for the regeneration of cartilage tissue and treatment of osteoarthritis in both humans and animals. For safe and effective use of MSCs as therapeutic agents, quality control of the isolation and expansion methods as well as the final MSC product is of key importance. The aim of this study was to evaluate integrin α10β1 as a novel MSC biomarker to attest identity, purity and potency of MSC preparations. We found that MSCs, isolated from equine adipose tissue (AT) and selected using an antibody directed to integrin α10, expressed the stem cell markers CD44, CD90 and CD105, differentiated to chondrocytes, osteocytes and adipocytes and demonstrated immunomodulatory capacity as judged by suppression of T-cell proliferation and expression of PGE2 . In addition, we found that integrin α10-selected equine AT-MSCs showed higher chondrogenic differentiation capacity, in pellet mass cultures, compared to unselected MSCs. Moreover, the integrin α10-selected fraction of MSCs showed significantly higher adhesion capacity to cartilage defects in ex vivo osteochondral explants compared to unselected MSCs demonstrating a higher ability of the α10-enriched MSCs to home to an osteochondral damage. Taken together, the results show that integrin α10β1 can identify a homogenous population of multipotent equine AT-MSCs with a high chondrogenic differentiation and immunomodulatory potency as well as homing capacity. Thus, we conclude that integrin α10β1 is a biomarker that can ensure quality, potency and consistency of MSC preparations for cartilage repair.

 

Keywords

Integrin α10β1, MSCs, Selection, Chondrogenesis, Immunomodulation

 

 


 

 

Cell Signal. 2019 Jan;53:212-223. doi: 10.1016/j.cellsig.2018.10.005. Epub 2018 Oct 9.

 

Interleukin-1β signaling in osteoarthritis - chondrocytes in focus.


Jenei-Lanzl Z, Meurer A, Zaucke F

(SP8)                     

 

Full Text

https://reader.elsevier.com/reader/sd/pii/S0898656818302547?token=AA68F37086062EA4A306C293725C82AD6994A8E3123A3F399C017ACAFA9BB95E2CAC0B5E9DA68FFD67A9B8E2FE02BA96

 

Abstract

Osteoarthritis (OA) can be regarded as a chronic, painful and degenerative disease that affects all tissues of a joint and one of the major endpoints being loss of articular cartilage. In most cases, OA is associated with a variable degree of synovial inflammation. A variety of different cell types including chondrocytes, synovial fibroblasts, adipocytes, osteoblasts and osteoclasts as well as stem and immune cells are involved in catabolic and inflammatory processes but also in attempts to counteract the cartilage loss. At the molecular level, these changes are regulated by a complex network of proteolytic enzymes, chemokines and cytokines (for review: [1]). Here, interleukin-1 signaling (IL-1) plays a central role and its effects on the different cell types involved in OA are discussed in this review with a special focus on the chondrocyte.  

 

PMID: 30312659 DOI: 10.1016/j.cellsig.2018.10.005

 

 


 

 

Int J Mol Sci. 2019 Jan 23;20(3). pii: E484. doi: 10.3390/ijms20030484.

 

The Importance of Physioxia in Mesenchymal Stem Cell Chondrogenesis and the Mechanisms Controlling Its Response.

 

Pattappa G, Johnstone B, Zellner J, Docheva D, Angele P.

(SP7)                     

 

Full Text

https://www.mdpi.com/1422-0067/20/3/484

 

Abstract

Articular cartilage covers the surface of synovial joints and enables joint movement. However, it is susceptible to progressive degeneration with age that can be accelerated by either previous joint injury or meniscectomy. This degenerative disease is known as osteoarthritis (OA) and it greatly affects the adult population. Cell-based tissue engineering provides a possible solution for treating OA at its earliest stages, particularly focal cartilage lesions. A candidate cell type for treating these focal defects are Mesenchymal Stem Cells (MSCs). However, present methods for differentiating these cells towards the chondrogenic lineage lead to hypertrophic chondrocytes and bone formation in vivo. Environmental stimuli that can stabilise the articular chondrocyte phenotype without compromising tissue formation have been extensively investigated. One factor that has generated intensive investigation in MSC chondrogenesis is low oxygen tension or physioxia (2⁻5% oxygen). In vivo articular cartilage resides at oxygen tensions between 1⁻4%, and in vitro results suggest that these conditions are beneficial for MSC expansion and chondrogenesis, particularly in suppressing the cartilage hypertrophy. This review will summarise the current literature regarding the effects of physioxia on MSC chondrogenesis with an emphasis on the pathways that control tissue formation and cartilage hypertrophy.

 

Keywords

chondrogenesis; early osteoarthritis; hypertrophy; hypoxia; hypoxia inducible factors; mesenchymal stem cells

 

 

 

 


Publications in 2018


 

 

Sci Rep. 2018 Jun 25;8(1):9645. doi: 10.1038/s41598-018-27927-8.

 

TNF inhibits catecholamine production from induced sympathetic neuron-like cells in rheumatoid arthritis and osteoarthritis in vitro

 

Markus Herrmann, Sven Anders, Rainer H. Straub & Zsuzsa Jenei-Lanzl

(SP8)                     

 

Full Text

https://www.nature.com/articles/s41598-018-27927-8.pdf


Abstract

Synovial adipose stem cells (sASC) can be differentiated into catecholamine-expressing sympathetic neuron-like cells to treat experimental arthritis. However, the pro-inflammatory tumor necrosis factor (TNF) is known to be toxic to catecholaminergic cells (see Parkinson disease), and this may prevent anti-inflammatory effects in inflamed tissue. We hypothesized that TNF exhibits inhibitory effects on human differentiated sympathetic tyrosine hydroxylase-positive (TH+) neuron-like cells. For the first time, iTH+ neuron-like sympathetic cells were generated from sACSs of rheumatoid arthritis (RA) and osteoarthritis (OA) synovial tissue. Compared to untreated controls in both OA and RA, TNF-treated iTH+ cells demonstrated a weaker staining of catecholaminergic markers in cell cultures of RA/OA patients, and the amount of produced noradrenaline was markedly lower. These effects were reversed by etanercept. Exposure of iTH+ cells to synovial fluid of RA patients showed similar inhibitory effects. In mixed synovial cells, significant effects of TNF on catecholamine release were observed only in OA. This study shows that TNF inhibits iTH+ synovial cells leading to the decrease of secreted noradrenaline. This might be a reason why discovered newly appearing TH+ cells in the synovium are not able to develop their possible full anti-inflammatory role in arthritis.  

 

Keywords

Bone histomorphometry; Subchondral bone; Microcomputed tomography; 31 Osteoarthritis; Calcified cartilage 

 

PMID: 29941879 PMCID: PMC6018168 DOI: 10.1038/s41598-018-27927-8

 

 


 

 

Biochim Biophys Acta Mol Basis Dis. 2018 Mar;1864(3):851-859. doi: 10.1016/j.bbadis.2017.12.024. Epub 2017 Dec 19.

 

Extracellular matrix content and WNT/β-catenin levels of cartilage determine the chondrocyte response to compressive load.

 

Praxenthaler H1, Krämer E1, Weisser M1, Hecht N1, Fischer J1, Grossner T2, Richter W3.

(SP3)

 

Pubmed Link:

https://www.ncbi.nlm.nih.gov/pubmed/29277327


Abstract

During osteoarthritis (OA)-development extracellular matrix (ECM) molecules are lost from cartilage, thus changing gene-expressionmatrix synthesis and biomechanical competence of the tissue. Mechanical loading is important for the maintenance of articular cartilage; however, the influence of an altered ECM content on the response of chondrocytes to loading is not well understood, but may provide important insights into underlying mechanisms as well as supplying new therapies for OA. Objective here was to explore whether a changing ECM-content of engineered cartilage affects major signaling pathways and how this alters the chondrocyte response to compressive loading. Activity of canonical WNT-, BMP-, TGF-β- and p38-signaling was determined during maturation of human engineered cartilage and followed after exposure to a single dynamic compression-episode. WNT/β-catenin- and pSmad1/5/9-levels declined with increasing ECM-content of cartilage. While loading significantly suppressed proteoglycan-synthesis and ACAN-expression at low ECM-content this catabolic response then shifted to an anabolic reaction at high ECM-content. A positive correlation was observed between GAG-content and load-induced alteration of proteoglycan-synthesis. Induction of high β-catenin levels by the WNT-agonist CHIR suppressed load-induced SOX9- and GAG-stimulation in mature constructs. In contrast, the WNT-antagonist IWP-2 was capable of attenuating load-induced GAG-suppression in immature constructs. In conclusion, either ECM accumulation-associated or pharmacologically induced silencing of WNT-levels allowed for a more anabolic reaction of chondrocytes to physiological loading. This is consistent with the role of proteoglycans in sequestering WNT-ligands in the ECM, thus reducing WNT-activity and also provides a novel explanation of why low WNT-activity in cartilage protects from OA-development in mechanically overstressed cartilage.

Copyright © 2017 Elsevier B.V. All rights reserved.

 

KEYWORDS:

Cell signaling; Chondrocyte; Mechanical loading; Osteoarthritis; SOX9

 

PMID: 29277327 DOI: 10.1016/j.bbadis.2017.12.024

 

 


 

 

Int J Mol Sci. 2018 Jan 26; 19 (2). pii: E367. doi: 10.3390/ijms19020367.

 

Do Neuroendocrine Peptides and Their Receptors Qualify as Novel Therapeutic Targets in Osteoarthritis?

 

Grässel S1, Muschter D2.

(SP4)

                         

Full Text

ijms-19-00367.pdf

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Abstract

Joint tissues like synovium, articular cartilage, meniscus and subchondral bone, are targets for neuropeptides. Resident cells of these tissues express receptors for various neuroendocrine-derived peptides including proopiomelanocortin (POMC)-derived peptides, i.e., α-melanocyte-stimulating hormone (α-MSH), adrenocorticotropin (ACTH) and β-endorphin (β-ED), and sympathetic neuropeptides like vasoactive intestinal peptide (VIP) and neuropeptide y (NPY). Melanocortins attained particular attention due to their immunomodulatory and anti-inflammatory effects in several tissues and organs. In particular, α-MSH, ACTH and specific melanocortin-receptor (MCR) agonists appear to have promising anti-inflammatory actions demonstrated in animal models of experimentally induced arthritis and osteoarthritis (OA). Sympathetic neuropeptides have obtained increasing attention as they have crucial trophic effects that are critical for joint tissue and bone homeostasis. VIP and NPY are implicated in direct and indirect activation of several anabolic signaling pathways in bone and synovial cells. Additionally, pituitary adenylate cyclase-activating polypeptide (PACAP) proved to be chondroprotective and, thus, might be a novel target in OA. Taken together, it appears more and more likely that the anabolic effects of these neuroendocrine peptides or their respective receptor agonists/antagonists may be exploited for the treatment of patients with inflammatory and degenerative joint diseases in the future.

 

KEYWORDS

NPY; PACAP; VIP; alpha-MSH; neuroendocrine; osteoarthritis; proopiomelanocortin

 

PMID: 29373492

 

 


 

 

J Cell Physiol. 2018 Jan;233(1):699-711. doi: 10.1002/jcp.25933. Epub 2017 May 19.

 

Global chondrocyte gene expression after a single anabolic loading period: Time evolution and re-inducibility of mechano-responses.

 

Scholtes S1, Krämer E1, Weisser M1, Roth W1, Luginbühl R2, Grossner T3, Richter W1. 

(SP3)

 

Pubmed Link:

https://www.ncbi.nlm.nih.gov/pubmed/28369921


Abstract

Aim of this study was a genome-wide identification of mechano-regulated genes and candidate pathways in human chondrocytes subjected to a single anabolic loading episode and characterization of time evolution and re-inducibility of the response. Osteochondral constructs consisting of chondrocyte-seeded collagen-scaffold connected to β-tricalcium-phosphate were pre-cultured for 35 days and subjected to dynamic compression (25% strain, 1 Hz, 9 × 10 min over 3 hr) before microarray-profiling was performed. Proteoglycan synthesis was determined by 35 S-sulfate-incorporation over 24 hr. Cell viability and hardness of constructs were unaltered by dynamic compression while proteoglycan synthesis was significantly stimulated (1.45-fold, p = 0.016). Among 115 significantly regulated genes, 114 were up-regulated, 48 of them twofold. AP-1-relevant transcription factors FOSB and FOS strongly increased in line with elevated ERK1/2-phosphorylation and rising MAP3K4 expression. Expression of proteoglycan-synthesizing enzymes CHSY1 and GALNT4 was load-responsive as were factors associated with the MAPK-, TGF-β-, calcium-, retinoic-acid-, Wnt-, and Notch-signaling pathway which were significantly upregulated SOX9, and BMP6 levels rose significantly also after multiple loading episodes at daily intervals even at the 14th cycle with no indication for desensitation. Canonical pSmad2/3 and pSmad1/5/9-signaling showed no consistent regulation. This study associates novel genes with mechanoregulation in chondrocytes, raising SOX9 protein levels with anabolic loading and suggests that more pathways than so far anticipated apparently work together in a complex network of stimulators and feedback-regulators. Upregulation of mechanosensitive indicators extending differentially into the resting time provides crucial knowledge to maximize cartilage matrix deposition for the generation of high-level cartilage replacement tissue.

© 2017 Wiley Periodicals, Inc.

 

KEYWORDS:

BMP signalling; MAPK; SOX9; TGF-β signaling; proteoglycan synthesis

 

PMID: 28369921 DOI: 10.1002/jcp.25933

 

 

 

 


Publications in 2017


 

 

J Biosci Bioeng. 2017 Apr;123(4):512-522. doi: 10.1016/j.jbiosc.2016.11.002. Epub 2016 Nov 28.

 

Cell compaction influences the regenerative potential of passaged bovine articular chondrocytes in an ex vivo cartilage defect model.

 

Schmutzer M, Aszodi A.

(SP1)                     

 

Full Text

https://www.sciencedirect.com/science/article/pii/S1389172316305011?via%3Dihub

 

Abstract

The loss and degradation of articular cartilage tissue matrix play central roles in the process of osteoarthritis (OA). New models for evaluating cartilage repair/regeneration are thus of great value for transferring various culture systems into clinically relevant situations. The repair process can be better monitored in ex vivo systems than in in vitro cell cultures. I have therefore established an ex vivo defect model prepared from bovine femoral condyles for evaluating cartilage repair by the implantation of cells cultured in various ways, e.g., monolayer-cultured cells or suspension or pellet cultures of articular bovine chondrocytes representing different cell compactions with variable densities of chondrocytes. I report that the integrin subunit α10 was significantly upregulated in suspension-cultured bovine chondrocytes at passage P2 compared with monolayer-cultured cells at P1 (p = 0.0083) and P2 (p < 0.05). Suspension-cultured cells did not promote cartilage repair when compared with implanted monolayer-cultured chondrocytes and pellets: 24.0 ± 0.66% for suspension cells, 46.4 ± 2.9% for monolayer cells, and 127.64 ± 0.90% for pellets (p < 0.0001) of the original defect volume (percentage of defect). Additional cultivation with chondrogenesis-promoting growth factors TGF-β1 and BMP-2 revealed an enhancing effect on cartilage repair in all settings. The advantage and innovation of this system over in vitro differentiation (e.g., micromass, pellet) assays is the possibility of examining and evaluating cartilage regeneration in an environment in which implanted cells are embedded within native surrounding tissue at the defect site. Such ex vivo explants might serve as a better model system to mimic clinical situations.

 

Keywords

BMP2; Cartilage repair; Cell compaction; Chondrocytes; Ex vivo defect model; Growth factors; Passaging; Pellets; Suspension culture; TGFbeta1 

 

 


 

 

Int J Mol Sci. 2017 Apr 28; 18 (5). pii: E931. doi: 10.3390/ijms18050931

 

Peripheral Nerve Fibers and Their Neurotransmitters in Osteoarthritis Pathology.

 

Grässel S1, Muschter D2.

(SP4)

 

Full Text

ijms-18-00931.pdf

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Abstract

The importance of the nociceptive nervous system for maintaining tissue homeostasis has been known for some time, and it has also been suggested that organogenesis and tissue repair are under neuronal control. Changes in peripheral joint innervation are supposed to be partly responsible for degenerative alterations in joint tissues which contribute to development of osteoarthritis. Various resident cell types of the musculoskeletal system express receptors for sensory and sympathetic neurotransmitters, allowing response to peripheral neuronal stimuli. Among them are mesenchymal stem cells, synovial fibroblasts, bone cells and chondrocytes of different origin, which express distinct subtypes of adrenoceptors (AR), receptors for vasoactive intestinal peptide (VIP), substance P (SP) and calcitonin gene-related peptide (CGRP). Some of these cell types synthesize and secrete neuropeptides such as SP, and they are positive for tyrosine-hydroxylase (TH), the rate limiting enzyme for biosynthesis of catecholamines. Sensory and sympathetic neurotransmitters are involved in the pathology of inflammatory diseases such as rheumatoid arthritis (RA) which manifests mainly in the joints. In addition, they seem to play a role in pathogenesis of priori degenerative joint disorders such as osteoarthritis (OA). Altogether it is evident that sensory and sympathetic neurotransmitters have crucial trophic effects which are critical for joint tissue and bone homeostasis. They modulate articular cartilage, subchondral bone and synovial tissue properties in physiological and pathophysiological conditions, in addition to their classical neurological features.

 

KEYWORDS:

CGRP; adrenoceptors; cartilage; neurotransmitters; osteoarthritis; peripheral nervous system; subchondral bone; substance P

 

PMID: 28452955

PMCID: PMC5454844

 

 


 

 

Cartilage Vol. 2  Chapter 10 Page 191-227 Springer February 2017 

 

The Sensory and Sympathetic Nervous System in Cartilage Physiology and Pathophysiology

 

Grässel S, Straub RH, Jenei-Lanzl Z

(SP8)               

 

Full Text

https://link.springer.com/chapter/10.1007/978-3-319-45803-8_9

ISBN 978-3-319-45801-4

DOI   10.1007/978-3-319-45803-8_9

 

Abstract

The peripheral nervous system is critically involved in metabolism of joint tissue and intervertebral disks (IVD). Nerve fibers of sympathetic and sensory origin innervate synovial tissue and subchondral bone of diarthrodial joints. In pathophysiological situations as in osteoarthritis (OA), rheumatoid arthritis (RA), and IVD degeneration, innervation patterns of sympathetic and sensory nerve fibers are partly altered in joint tissue and IVD.

Various resident cell types of the musculoskeletal system express receptors for sensory and sympathetic neurotransmitters allowing response to neuronal stimuli. Among them are mesenchymal stem cells, synovial fibroblasts, bone cells, and different types of chondrocytes, which express distinct subtypes of adrenoceptors, receptors for vasoactive intestinal peptide (VIP), for substance P (SP), and calcitonin gene-related peptide (CGRP). Some of these cell types even synthesize neuropeptides such as SP, and they are positive for tyrosine hydroxylase (TH), the rate limiting enzyme for biosynthesis of catecholamines. During endochondral ossification in embryonic limb development, sensory and sympathetic neurotransmitters modulate osteo-chondrogenic differentiation of mesenchymal progenitor cells, vascularization, and matrix differentiation indicating a distinct role in skeletal growth and possible limb regeneration processes. In adults, sensory and sympathetic neurotransmitters are involved in pathology of inflammatory diseases as rheumatoid arthritis which manifests mainly in joints. In addition, they might play a role in pathogenesis of a priori degenerative joint disorders, as osteoarthritis and intervertebral disk degeneration.

Altogether it became evident that sensory and sympathetic neurotransmitters have crucial trophic effects which are critical for proper limb formation during embryonic skeletal growth. In adults, they modulate articular cartilage, subchondral bone and synovial tissue homeostasis, and physiological and pathophysiological conditions, in addition to their classical neurological features.

 

Keywords

Nerve Fiber Nerve Growth Factor Articular Cartilage Vasoactive Intestinal Peptide Annulus Fibrosus