Candeliere G A, Glorieux F H, Prud'homme J, St-Arnaud R
Genetics Unit, Shriners Hospital, Montreal, QC, Canada.
N Engl J Med. 1995 Jun 8;332(23):1546-51. doi: 10.1056/NEJM199506083322304.
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 alpha subunit of the stimulatory guanine-nucleotide-binding protein (GS alpha) linked to adenylate cyclase have recently been described in bone cells from patients with the McCune-Albright syndrome and fibrous dysplasia.
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.
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 alpha gene mutations and were found to express these mutations in bone.
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.
骨纤维结构不良的特征是骨髓纤维化严重且骨转换率增加。骨纤维结构不良的病变类似于在过表达c-fos原癌基因的转基因小鼠长骨中所描述的病变。最近在McCune-Albright综合征和骨纤维结构不良患者的骨细胞中发现了与腺苷酸环化酶相关的刺激性鸟嘌呤核苷酸结合蛋白（GSα）α亚基的激活突变。
我们使用原位杂交技术来测定两名正常受试者、八名骨纤维结构不良患者以及六名以高骨转换率为特征的其他骨病患者的骨活检标本中c-fos的表达水平。所用探针对应于c-fos基因的第四外显子。
在所有八名骨纤维结构不良患者的骨病变中均检测到高水平的c-fos表达。在正常受试者的骨标本或骨纤维结构不良患者的正常骨标本中未检测到c-fos的表达。在发育异常病变中表达c-fos的细胞为成纤维细胞，分布于骨髓腔。在其他骨病患者的活检标本中检测到极低水平的c-fos表达。对一名多骨型骨纤维结构不良患者和一名McCune-Albright综合征患者进行了先前描述的GSα基因突变检测，发现他们的骨中表达这些突变。
c-fos原癌基因表达增加，可能是腺苷酸环化酶活性增加的结果，在骨纤维结构不良患者骨病变的发病机制中可能起重要作用。
