Inducement of mitogen-activated protein kinases in frozen shoulders
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Original article Inducement of mitogen-activated protein kinases in frozen shoulders KATSUAKI KANBE1, KAZUHIKO INOUE1, YASUO INOUE1, and QIAN CHEN2 1
Department of Orthopaedic Surgery, Tokyo Women’s Medical University, Medical Center East, 2-1-10 Nishiogu, Arakawa, Tokyo 116-8567, Japan Department of Orthopaedics, Brown Medical School/Rhode Island Hospital, Providence, RI, USA
2
Abstract Background. Mitogen-activated protein (MAP) kinases are well-known molecules that play key roles in mechanical stress signals during skeletal development. To test our hypothesis that the synovium in frozen shoulders is induced by MAP kinases, immunohistochemical analyses for detecting expression and signal transduction of MAP kinases were performed in synovial tissue obtained from the rotator interval (RI) in frozen shoulders. Methods. Synovial tissues were examined from 10 frozen shoulder patients with a mean age of 55.4 years (46–62 years). Synovial tissues between the long head of the biceps tendon (LHB) and the RI in frozen shoulders were stained with hematoxylin and eosin (H&E) and then examined with immunohistochemical staining. Extracellular signal-regulated (ERK), the Jun N-terminal (JNK), and p38 mitogen-activated protein (MAP) kinases, nuclear factor κB (NF-κB), p50, CD29 (β1-integrin), matrix metalloproteinase (MMP)-3, interleukin-6 (IL-6), CD56, CD68, S-100, and vascular endothelial growth factor (VEGF) were analyzed to detect expression patterns. Results. H&E showed vascular proliferation with fibrin and fibrous tissue in the synovium of frozen shoulders. ERK was expressed in the epithelial cells of vascular tissue, and JNK was expressed strongly in the interstitial cells around vascular tissue; p38 MAPK was not expressed. NF-κB was expressed in vascular tissue, and IL-6 was expressed around vascular tissue. CD29 (β1-integrin) was expressed in vascular tissue and in superficial cells of synovial tissue. MMP-3 and VEGF were expressed on the surface layer of synovial tissue and vascular tissue, and CD68 was expressed on the surface layer. Nerverelated proteins, CD56 and S-100, were expressed weakly. Conclusions. Mechanical stress on the LHB and RI in the shoulder may induce ERK and JNK to express NF-κB by CD29 to develop capsule contracture, producing MMP-3, IL6, and VEGF.
Offprint requests to: K. Kanbe Received: May 9, 2008 / Accepted: October 7, 2008
Introduction Duplay first reported frozen shoulder nearly 150 years ago, but the cause of this disease remains unclear.1 In 1934, Codman described the diagnostic criteria for frozen shoulder, which are the same today.2 Pain in the shoulder comes on slowly and is felt in the deltoid, one cannot sleep on the affected side, and there is a little local tenderness. The range of active and passive motions are restricted in terms of upward movement and rotation. Studies of cadavers and observations during open and arthroscopic surgery have identified the anatomical area predominantly involved in frozen shoulder to be the rotator interval, which contains the coracohumeral (CH)
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