INCREASED COLLAGEN-SYNTHESIS IN SKIN FIBROBLASTS FROM PATIENTS WITH PRIMARY HYPERTROPHIC OSTEOARTHROPATHY - EVIDENCE FOR TRANS-ACTIVATIONALREGULATION OF COLLAGEN TRANSCRIPTION

Objective. To investigate collagen synthesis in skin fibroblasts from patients with primary hypertrophic osteoarthropathy (HOA), a disorder characterized clinically by skin thickening. Methods. Collagenase-dige stible protein, messenger RNA (mRNA) levels, and transcriptional activ ity of the alpha 1(I) procollagen gene were assessed in skin-derived f ibroblast lines. Results. Compared with fibroblasts from uninvolved sk in, fibroblasts from involved skin had elevated levels of collagen syn thesis and alpha 1(I) procollagen mRNA, and increased transcriptional activity of the alpha 1(I) procollagen promoter. Conclusion. Abnormali ties of collagen synthesis in fibroblasts from patients with primary H OA can be accounted for, at least in part, by a trans-activated upregu lation of collagen transcription.