title: Periostin, a novel marker of intramembranous ossification, is expressed in fibrous dysplasia and in c-Fos-overexpressing bone lesions.
abstract: Fibrous dysplasia is a benign bone disease caused by a mutation in the gene for the stimulatory guanine nucleotide-binding protein Gs alpha, leading to high cyclic adenosine monophosphate levels. Histologically, fibrous dysplasia is characterized by the production of fibrous tissue accompanied by the deposition of ectopic type I collagen and other bone-associated extracellular matrix proteins, as well as by irregular woven intramembranous bone onto which type I collagen-containing Sharpey fibers are often attached. Fibrous dysplasia is also characterized by high expression of c-Fos/c-Jun, known targets for cyclic adenosine monophosphate signaling. In this study, we examined the expression of the bone-related extracellular matrix protein, periostin, and its known receptor, integrin alpha v beta 3 (CD51/61), in normal bones as well as in fibrous dysplasia. Immunohistochemistry and in situ hybridization studies revealed that periostin was expressed in the extracellular matrix during intramembranous but not endochondral ossification, as well as in the fibrous component of fibrous dysplasia; and all cells adjacent to periostin-positive regions expressed CD51/61. Importantly, periostin was abundantly localized to Sharpey fibers. To investigate the contribution of c-Fos, we examined transgenic mice overexpressing c-fos, which develop sclerotic lesions closely resembling those found in fibrous dysplasia. In all lesions, transformed osteoblasts expressed high levels of periostin, whereas normal osteoblasts did not. Our results show that periostin is a novel marker for intramembranous ossification, and is a good candidate as a diagnostic tool and/or a therapeutic target in fibrous dysplasia. Moreover, the Gs alpha-cyclic adenosine monophosphate-c-Fos pathway might represent one mechanism of periostin up-regulation in fibrous dysplasia, resulting in altered collagen fibrillogenesis characteristic of this disease.
authors.affiliation: Department of Human Pathology, Graduate School of Medicine, the University of Tokyo, Tokyo 113-0033, Japan.
authors.forename: Takeshi G
authors.initials: TG
authors.lastname: Kashima
authors.forename: Takashi
authors.initials: T
authors.lastname: Nishiyama
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Shimazu
authors.forename: Masashi
authors.initials: M
authors.lastname: Shimazaki
authors.forename: Isao
authors.initials: I
authors.lastname: Kii
authors.forename: Agamemnon E
authors.initials: AE
authors.lastname: Grigoriadis
authors.forename: Masashi
authors.initials: M
authors.lastname: Fukayama
authors.forename: Akira
authors.initials: A
authors.lastname: Kudo
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D001842:Bone and Bones / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D002648:Child; D002675:Child, Preschool; D005109:Extracellular Matrix; D005260:Female; D005357:Fibrous Dysplasia of Bone / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D009999:Ossification, Heterotopic / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism*
chemical_list: D015815:Cell Adhesion Molecules; D039302:Integrin alphaVbeta3; C512835:POSTN protein, human; D016760:Proto-Oncogene Proteins c-fos