Role of the sensory nervous system in osteoarthritis pathology
Final Report Abstract
About 655 million persons worldwide are affected by OA, which is a complex multifactorial disease, that can affect all synovial joint tissues and is one of the leading causes of excruciating chronic pain and disability in the elderly. Joint impairment is due to articular cartilage degeneration, subchondral bone sclerosis, joint deformation and synovial inflammation among other pathologies. No actual therapy has been successful to modify disease progression long-term indicating an immense clinical need for developing novel disease-modifying drugs (DMOADs) or regenerative therapies. Besides their classical function in nociception, SP and αCGRP have extra functions in the musculoskeletal system, which can be summarized as trophic effects influencing the metabolism of the target cells. Contrary to the physiological situation, information on the effects of SP and αCGRP in cartilage and subchondral bone under OA conditions is sparse. Sensory nerve fibers and their neurotransmitters are crucial neuronal effectors regulating cartilage and bone physiology. Numerous resident cells of the osteoarticular system have receptors for sensory neurotransmitters and are able to respond to these stimuli. It becomes more and more evident that neuronal signaling critically influences tissue regeneration, i.e., after bone, osteochondral and meniscal traumata and tendon/ligament ruptures. A better understanding of changes in sensory neuropeptide supply in the context of increased proinflammatory and a lack of regenerative signaling factors might lead to novel strategies to halt OA progression and in improved therapies for the treatment of synovitis and cartilage and osteochondral lesions.
Publications
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Induction of ALP and MMP9 activity facilitates invasive behavior in heterogeneous human BMSC and HNSCC 3D spheroids. FASEB J. 2019 Nov;33(11):11884-11893
Wessely A, Waltera A, Reichert TE, Stöckl S, Grässel S, Bauer RJ
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hBMSC-Derived Extracellular Vesicles Attenuate IL-1β-Induced Catabolic Effects on OA-Chondrocytes by Regulating Pro-inflammatory Signaling Pathways. Front Bioeng Biotechnol. 2020 Dec 14;8:603598
Li S, Stöckl S, Lukas C, Götz J, Herrmann M, Federlin M, Grässel S
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SOX9 Knockout Induces Polyploidy and Changes Sensitivity to Tumor Treatment Strategies in a Chondrosarcoma Cell Line. Int J Mol Sci. 2020 Oct 15;21(20):7627
Stöckl S, Lindner G, Li S, Schuster P, Haferkamp S, Wagner F, Prodinger PM, Multhoff G, Boxberg M, Hillmann A, Bauer RJ, Grässel S
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Curcumin-primed human BMSC-derived extracellular vesicles reverse IL-1β-induced catabolic responses of OA chondrocytes by upregulating miR-126- 3p. Stem Cell Res Ther. 2021 Apr 29;12(1):252
Li S, Stöckl S, Lukas C, Herrmann M, Brochhausen C, König MA, Johnstone B, Grässel S
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Substance P and Alpha-Calcitonin Gene-Related Peptide Differentially Affect Human Osteoarthritic and Healthy Chondrocytes. Front Immunol. 2021 Aug 27;12:722884
Stöckl S, Eitner A, Bauer RJ, König M, Johnstone B, Grässel S
