Y. Wegrowski et al., ALTERATION OF MATRIX MACROMOLECULE SYNTHESIS BY FIBROBLASTS FROM A PATIENT WITH PACHYDERMOPERIOSTOSIS, Journal of investigative dermatology, 106(1), 1996, pp. 70-74
Pachydermoperiostosis (primary hypertrophic osteoarthropathy) is a ver
y rare genetic disease characterized by pachydermia, periostosis, arth
ralgia, and finger clubbing. Its pathophysiology is still unclear, but
previous studies have reported connective tissue hypertrophy in the s
kin of these patients. We investigated the synthesis of collagen, fibr
onectin, and proteoglycans by fibroblasts from affected and unaffected
skin from one patient with pachydermoperiostosis and four normal dono
rs. We found that collagen synthesis was largely decreased in fibrobla
sts from the diseased skin, whereas the synthesis of the small dermata
n-sulfate-containing proteoglycan decorin strongly increased. Fibrobla
sts from the unaffected skin of the patient exhibited syntheses of the
se macromolecules similar to control fibroblasts from healthy donors.
Northern blot and dot blot analyses showed decreased pro alpha(1)(I) c
ollagen in patient's affected and unaffected skin fibroblasts whereas
increased decorin mRNA levels were found in fibroblasts from the patie
nt's affected skin. No change in cell proliferation was observed. Thes
e data demonstrate an alteration of fibroblast biosynthetic activity i
n the skin lesions of pachydermoperiostosis, which may be responsible,
at least in part, for the patient's phenotype.