Inducement of mitogen-activated protein kinases in frozen shoulders

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.

Mechanical stress on the LHB and RI in the shoulder may induce ERK and JNK to express NF-kappaB by CD29 to develop capsule contracture, producing MMP-3, IL-6, and VEGF.

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 kappaB (NF-kappaB), p50, CD29 (beta(1)-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.

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-kappaB was expressed in vascular tissue, and IL-6 was expressed around vascular tissue. CD29 (beta1-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. Nerve-related 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-kappaB by CD29 to develop capsule contracture, producing MMP-3, IL-6, and VEGF.