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Previous Volume 332:1546-1551 June 8, 1995 Number 23 Next

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ABSTRACT

Background Fibrous dysplasia is characterized by intense marrow fibrosis and increased rates of bone turnover. The lesions of fibrous dysplasia resemble those described in the long bones of transgenic mice overexpressing the c-fos proto-oncogene. Activating mutations in the subunit of the stimulatory guanine-nucleotide–binding protein (G_s) linked to adenylate cyclase have recently been described in bone cells from patients with the McCune–Albright syndrome and fibrous dysplasia.

Methods We used in situ hybridization to determine the level of expression of c-fos in bone-biopsy specimens from two normal subjects, eight patients with fibrous dysplasia, and six patients with other bone disorders characterized by high rates of bone turnover. The probe used corresponded to the fourth exon of the c-fos gene.

Results High levels of c-fos expression were detected in the bone lesions from all eight patients with fibrous dysplasia. No expression of c-fos was detected in bone specimens from the normal subjects or from specimens of normal bone obtained from patients with fibrous dysplasia. The cells that expressed c-fos in the dysplastic lesions were fibroblastic and populated the marrow space. A very low level of c-fos expression was detected in the biopsy specimens from the patients with other bone diseases. One patient with polyostotic fibrous dysplasia and one patient with the McCune–Albright syndrome were tested for the previously described Gs gene mutations and were found to express these mutations in bone.

Conclusions Increased expression of the c-fos proto-oncogene, presumably a consequence of increased adenylate cyclase activity, may be important in the pathogenesis of the bone lesions in patients with fibrous dysplasia.

Source Information

From the Genetics Unit, Shriners Hospital (J.P.), and the Departments of Surgery (G.A.C., F.H.G., R.S.) and Human Genetics (F.H.G., R.S.), McGill University — both in Montreal.

Address reprint requests to Dr. St.-Arnaud at the Genetics Unit, Shriners Hospital, 1529 Cedar Ave., Montreal, QC H3G 1A6, Canada.

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