PILOT 2 CHEMOKINE EXPRESSION REGULATION IN HUMAN SUBACROMIAL BURSA

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 趋化因子在人肩峰下囊中的表达及调控 摘要： 最近的研究证实，在肩峰下滑囊滑膜细胞中存在趋化因子(肿瘤坏死因子α、白介素1、白介素6、环氧合酶2)，其中一些在滑囊炎组织中表达上调。这些研究已经确定了SDF-1的一个新的作用，SDF-1是一种强大的趋化和血管生成因子，可以刺激炎症细胞的招募。在培养的法氏囊滑膜细胞中，SDF-1的表达可能受到机械、环境和化学刺激的诱导和调节。目前，这些刺激导致肩峰下炎症和法氏囊滑膜细胞SDF-1表达的机制尚不清楚。本研究的目的将是确定外界刺激诱导SDF-1的机制。对SDF-1表达重要的细胞信号过程将使用信号转导抑制剂进行评估。将使用前列腺素、环氧合酶-2抑制剂和皮质类固醇进一步研究抑制的途径。最后，为了开发对肩峰下滑囊炎的靶向抑制，将检测包括小干扰RNA(SiRNA)在内的SDF-1抑制剂对法氏囊滑膜细胞SDF-1表达的潜在作用。由于肩痛的发生率很高(每年超过600万次办公室就诊)，以及普遍使用具有显著副作用风险的非选择性药物(非类固醇抗炎药和类固醇)，该项目在治疗肩部撞击综合征方面具有重要的临床意义，肩部撞击综合征是最常见的肌肉骨骼疾病之一。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Chemokine expression and regulation in human subacromial bursa Abstract: Recent investigations have identified the presence of chemokines (tumor necrosis factor alpha, interleukin 1, interleukin 6, cyclooxygenases (COX-2) in synoviocytes of the subacromial bursa, several of which are up-regulated in bursitis tissue compared to normal controls. These studies have identified a novel role for SDF-1, a potent chemotactic and angiogenic factor that stimulates recruitment of inflammatory cells. The expression of SDF-1 in the bursal synoviocyte in culture may be induced and regulated by mechanical, environmental and chemical stimuli. Currently, the mechanisms by which these stimuli lead to subacromial inflammation and SDF-1 expression in the bursal synoviocyte are unknown. The goal of the present study will be to determine the mechanisms of SDF-1 induction by external stimuli. Cell signaling processes important for SDF-1 expression will be assessed using signal transduction inhibitors. The pathways of inhibition will be further examined using prostaglandins, cox-2 inhibitors, and corticosteroids. Finally, in an effort to develop targeted inhibition of subacromial bursitis, the potential role for SDF-1 inhibitors including small interfering RNA (siRNA) on SDF-1 expression in the bursal synoviocyte will be examined. Due to the high prevalence of shoulder pain (over 6 million office visits per year) and the common use of non-selective pharmacologic agents which carry significant risk of side effects (NSAIDs and steroids), this project has important clinical relevance in the treatment of shoulder impingement syndrome, one of the most common musculoskeletal diseases.