权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Role of the sensory nervous system in osteoarthritis pathology

感觉神经系统在骨关节炎病理学中的作用

基本信息

批准号：
279910683
负责人：
Professorin Dr. Susanne Grässel
金额：
--
依托单位：
Abteilung Experimentelle Orthopädie
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2015
资助国家：
德国
起止时间：
2014-12-31 至 2020-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/279910683?language=en
关键词：
Role sensory nervous system osteoarthritis

项目摘要

Osteoarthritis (OA), a degenerative, slowly progressive synovial joint disease represents the leading cause of disability and chronic pain in the elderly. OA is a failure of all joint tissues, including the articular cartilage and the subchondral bone, and is initiated by multiple risk factors. To date pharmacological interventions can only relieve pain, whilst cell- and compound based therapies have limited success in the regeneration of damaged tissues. Thus, there is a need for identification of novel targets for diagnostic and therapeutic approaches to improve the treatment and life quality of OA patients. The joints are innervated by calcitonin gene-related peptide (alpha CGRP)- and substance P (SP) positive sensory nerve fibers which are a potential source of tibial-femoral pain during pathological changes in osteoarthritis. Alteration of sensory joint innervation might be partly responsible for degenerative changes which contribute to development of osteoarthritis. We pose following questions: 1. How do alpha CGRP- and SP-positive sensory nerves and neurotransmitters modulate OA pathology? 2. How do alpha CGRP- and SP affect articular chondrocyte metabolism and function? We assume that alpha CGRP neuropeptides are primarily anabolic whereas SP effects may be concentration dependent both: anabolic and catabolic. 3. How do nerve repellent factors contribute to changes in alpha CGRP- and SP-positive sensory nervous innervation density of the joint in OA pathology and how does inhibition of their effects modulate chondrocyte differentiation? We propose that expression of sensory nerve repellent factors is altered during OA pathology. 4. How do SP and alpha CGRP modulate metabolic activity and differentiation capacity of osteo-chondroprogenitor cells? We suggest that SP and alpha CGRP sensory neuronal pathways affect chondrogenic and osteogenic differentiation of BMSC oppositely. 5. How will a biomaterial-based therapy approach with both sensory neurotransmitters affect joint pathology? We assume that alpha CGRP will primarily be OA protective whereas SP will -concentration dependent- promote or alleviate OA pathogenesis when applied to the joint in early OA-pathology.

骨关节炎(OA)是一种退行性、进展缓慢的滑膜关节疾病，是老年人残疾和慢性疼痛的主要原因。骨关节炎是包括关节软骨和软骨下骨在内的所有关节组织的衰竭，由多种危险因素引发。到目前为止，药物干预只能缓解疼痛，而基于细胞和化合物的疗法在损伤组织再生方面的成功有限。因此，有必要为诊断和治疗方法确定新的靶点，以改善OA患者的治疗和生活质量。关节由降钙素基因相关肽(αCGRP)和P物质(SP)阳性感觉神经纤维支配，在骨关节炎的病理变化中，这些感觉神经纤维是胫股关节痛的潜在来源。感觉神经支配的改变可能是退行性改变的部分原因，而退行性改变有助于骨关节炎的发展。我们提出以下问题：1.α-CGRP和SP阳性的感觉神经和神经递质如何调节骨性关节炎的病理？2.α-CGRP和SP如何影响关节软骨细胞的代谢和功能？我们假设α-CGRP神经肽主要是合成代谢的，而SP的作用可能是浓度依赖的：合成代谢和分解代谢。3.在骨性关节炎病理中，神经排斥因子如何参与关节内α-CGRP和SP阳性感觉神经支配密度的改变，以及抑制其作用如何调节软骨细胞的分化？我们认为感觉神经排斥因子的表达在骨关节炎的病理过程中发生了改变。4.SP和α-CGRP如何调节骨软骨前体细胞的代谢活性和分化能力？提示P物质和α-降钙素基因相关肽感觉神经元通路对骨髓间充质干细胞向软骨和成骨分化的影响相反。5.具有两种感觉神经递质的生物材料治疗方法将如何影响关节病理？我们假设α-CGRP主要是对骨性关节炎具有保护作用，而在早期骨性关节炎的病理过程中，SP会促进或减轻骨性关节炎的发病。