Expression of growth factors, cytokines and matrix metalloproteinases in frozen shoulder

Frozen shoulder is a chronic fibrosing condition of capsule of the joint. T he predominant cells involved are fibroblasts and myofibroblasts which lay down a dense matrix of type-I and type-III collagen within the capsule. Thi s subsequently contracts leading to the typical features of pain and stiffn ess. Cytokines and growth factors regulate the growth and function of the f ibroblasts of connective tissue and remodelling of the matrix is controlled by the matrix metalloproteinases (MMPs) and their inhibitors. Our aim was to determine whether there was an abnormal expression or secret ion of cytokines, growth factors and MMPs in tissue samples from 14 patient s,vith frozen shoulder using the reverse transcription/polymerase chain rea ction (RT/PCR) technique and to compare the findings with those in tissue f rom four normal control shoulders and from five patients with Dupuytren's c ontracture. Tissue from frozen shoulders demonstrated the presence of mRNA for a large number of cytokines and growth factors although the frequency was only slig htly higher than in the control tissue. The frequency for a positive signal for the proinflammatory cytokines IL-1 beta and TNF-alpha and TNF-beta, wa s not as great as in the Dupuytren's tissue. The presence of mRNA for fibro genic growth factors was, however, more similar to that obtained in the con trol and Dupuytren's tissue. This correlated with the histological findings which in most specimens showed a dense fibrous tissue response with few ce lls other than mature fibroblasts and with very little evidence of any acti ve inflammatory cell process. Positive expressions of the mRNA for the MMPs were also increased, together with their natural inhibitor TIMP, The notab le exception compared with control and Dupuytren's tissue was the absence o f MMP-14, which is known to be a membrane-type MMP required for the activat ion of MMP-2 (gelatinase A). Understanding the control mechanisms which play a part in the pathogenesis of frozen shoulder may lead to the development of new regimes of treatment for this common, protracted and painful chronic fibrosing condition.