elastin and Osteopoikilosis

The recent progress made in understanding the normal biology and biochemistry of the extracellular matrix of human skin has allowed us to identify several different levels at which errors could be introduced into the structure and metabolism of collagen or elastin, the two major fibrillar components of the dermis. Currently, several heritable cutaneous diseases are known to display distinct collagen or elastin abnormalities. This article reviews some of the heritable cutaneous diseases and highlights those entities in which definite information on molecular alterations in collagen or elastin is available.

Topics: Adult; Collagen; Collagen Diseases; Cutis Laxa; Ehlers-Danlos Syndrome; Elastin; Fibroma; Humans; Male; Osteopoikilosis; Osteosclerosis; Pedigree; Skin Diseases; Skin Neoplasms

Buschke-Ollendorff syndrome (BOS; McKusick 16670) is an autosomal dominant connective-tissue disorder characterized by uneven osseous formation in bone (osteopoikilosis) and fibrous skin papules (dermatofibrosis lenticularis disseminata). We describe two patients in whom BOS occurred in an autosomal dominant inheritance pattern. The connective tissue of the skin lesions showed both collagen and elastin abnormalities by electron microscopy. Cultured fibroblasts from both patients produced 2-8 times more tropoelastin than normal skin fibroblasts in the presence of 10% calf serum. Involved skin fibroblasts of one patient produced up to eight times normal levels, whereas apparently uninvolved skin was also elevated more than threefold. In a second patient, whose involvement was nearly complete, elastin production was high in involved areas and less so in completely involved skin. Transforming growth factor-beta 1 (TGF beta 1), a powerful stimulus for elastin production, brought about similar relative increases in normal and BOS strains. Basic fibroblast growth factor, an antagonist of TGF beta 1-stimulated elastin production, was able to reduce elastin production in basal and TGF beta 1 stimulated BOS strains. Elastin mRNA levels were elevated in all patient strains, suggesting that Buschke-Ollendorff syndrome may result, at least in part, from abnormal regulation of extracellular matrix metabolism that leads to increased steady-state levels of elastin mRNA and elastin accumulation in the dermis.

Topics: Blotting, Southern; Cells, Cultured; Connective Tissue Diseases; Elastin; Female; Fibroblast Growth Factor 2; Fibroblasts; Humans; Male; Microscopy, Electron; Middle Aged; Nevus; Osteopoikilosis; Pedigree; Phenotype; RNA, Messenger; Skin; Skin Neoplasms; Syndrome; Transforming Growth Factor beta

A patient with dermatofibrosis lenticularis disseminata (Buschke-Ollendorff syndrome) was found to have a distinctive abnormality of the cutaneous elastic tissue. This abnormality, studied by histochemical and ultrastructural techniques, was characterized by the presence of hyalinized, thick fibers that entrapped normal bundles of collagen. Histochemically, these fibers stained like elastin but showed certain tinctorial characteristics of pre-elastin. Ultrastructurally, this elastin-like substance was composed of large clumps of electron-dense material with a fine fibrillar coating. The changes were sufficiently distinctive to be diagnosed by light microscopy.

Topics: Collagen; Elastic Tissue; Elastin; Female; Fibroma; Humans; Microscopy, Electron; Middle Aged; Osteopoikilosis; Skin; Skin Neoplasms; Syndrome

The Buschke-Ollendorff syndrome is an association of cutaneous lesions, dermatofibrosis lenticularis disseminata, with osteopoikilosis. This condition is inherited in an autosomal dominant pattern. In order to clarify the biochemical nature of the skin lesions, we have examined 12 patients with the Buschke-Ollendorf syndrome, representing 2 unrelated kindreds. Histologically, the lesions were characterized by excessive amounts of unusually broad, interlacing elastic fibers in the dermis. Digestion of skin secretions with pancreatic elastase completely removed these fibers. Electron microscopy of the dermis further revealed markedly branched elastic fibers without fragmentation. The accumulation of elastin in the skin was also demonstrated by measurements of desmosine employing a radioimmunoassay. The desmosine content of the skin lesions increased 3- to 7-fold when compared to the skin either from healthy controls or from uninvolved skin adjacent to a lesion. The results indicate that the skin lesions of the Buschke-Ollendorff syndrome are connective tissue nevi of the elastin type. Cell cultures from these patients may provide a convenient model to study the control mechanisms involved in elastin metabolism.

Topics: Desmosine; Elastic Tissue; Elastin; Fibroma; Humans; Osteopoikilosis; Osteosclerosis; Skin; Skin Neoplasms; Syndrome