Alterations in the expression of osteonectin, osteopontin and osteocalcin mRNAs during the development of skeletal tissues in vivo

Nakase, Takanobu; Takaoka, Kunio; Hirakawa, Kimiaki; Hirota, Seiichi; Takemura, Teiji; Onoue, Hitoshi; Takebayashi, Kimiko; Kitamura, Yukihiko; Nomura, Shosaku

doi:10.1016/s0169-6009(08)80056-6

Cited by 104 publications

(84 citation statements)

References 36 publications

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“…During skeletal development, immature osteoblasts express type I collagen and osteopontin mRNAs, but lack osteocalcin mRNA. 8,9 CAR-positive fibroblast-like cells in our study also showed this pattern of mRNA expression, detected by double stain of in situ hybridization and immunohistochemistry (Figures 5c-e and 6a-c). Taking these findings together, we concluded that the CAR-positive fibroblasts in the fracture callus were immature osteoblasts.…”

Section: Car In Fracture Healingsupporting

confidence: 80%

Coxsackievirus and adenovirus receptor (CAR)-positive immature osteoblasts as targets of adenovirus-mediated gene transfer for fracture healing

et al. 2003

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Section: Car In Fracture Healingsupporting

confidence: 80%

Coxsackievirus and adenovirus receptor (CAR)-positive immature osteoblasts as targets of adenovirus-mediated gene transfer for fracture healing

et al. 2003

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“…Our previous in vivo studies also showed that opn mRNA expression is closely related to physiological and pathological calci®cation (Hirota et al, 1993(Hirota et al, , 1995Nakase et al, 1994). We considered that the defective calci®cation in the homozygous (7/7) mice was due to the lack of opn gene expression.…”

Section: Discussionmentioning

confidence: 95%

Transcriptional regulation of osteopontin gene in vivo by PEBP2αA/CBFA1 and ETS1 in the skeletal tissues

et al. 1998

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“…2D). Tissue-specific transcription factor(s), which are only present in OC positive cells, may be involved in regulating the chimeric AV 2 TATA promoter. Furthermore, the addition of vitamin D did not affect the activity of any of the constructs shown in Fig.…”

Section: Androgen-independent Metastatic Human Prostate Cancer Cell Lmentioning

confidence: 99%

“…OC expression is transcriptionally regulated by vitamin D and limited exclusively to cells of the osteoblast lineage (2). OC is synthesized, secreted, and deposited by mature osteoblasts at the time of bone mineralization.…”

mentioning

confidence: 99%

Regulation of Human Osteocalcin Promoter in Hormone-independent Human Prostate Cancer Cells

Yeung¹,

Law²,

Yeh³

et al. 2002

Journal of Biological Chemistry

107

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Osteocalcin (OC) is a small (6 kDa) polypeptide whose expression was thought to be limited to mature osteoblasts. The discovery of OC expression in prostate cancer specimens led us to study the regulation of OC gene in androgen-independent metastatic human prostate PC3 cells. An 800-bp human OC (hOC) promoter-luciferase construct exhibited strong basal and vitamin D-induced activity in OC-positive human prostate and osteosarcoma cell lines. Through deletion analysis of the hOC promoter, the functional hierarchy of the cis-acting elements, OSE1, OSE2, and AP-1/VDRE, was established in PC3 cells (OSE1 > AP-1/VDRE > OSE2). By juxtaposing dimers of these 3 cis-elements, we produced a minimal hOC promoter capable of displaying high tissue specific activity in prostate cancer cells. Our study demonstrated three groups of transcription factors, Runx2, JunD/Fra-2, and Sp1, responsible for the high hOC promoter activity in PC3 cells by binding to the OSE2, AP-1/VDRE, and OSE1 elements, respectively. Among the three groups of transcription factors, the expression levels of Runx2 and Fra-2 are higher in the OC-positive PC3 cells and osteoblasts, compared with the OC-negative LNCaP cells. Interestingly, unlike the mouse OC promoter, the OSE1 site in hOC promoter is regulated by members of Sp1 family instead of the osteoblast-specific factor Osf1. The molecular basis for androgen-independent prostate cancer cells behaving like mature osteoblasts may be explained by the interplay and coordination of these transcription factors under the tight regulation of autocrine and paracrine mediators.Osteocalcin (OC) 1 is the major noncollagenous bone matrix protein expressed in bone (1). OC expression is transcriptionally regulated by vitamin D and limited exclusively to cells of the osteoblast lineage (2). OC is synthesized, secreted, and deposited by mature osteoblasts at the time of bone mineralization. It serves as a phenotypic marker for mature osteoblasts (3). Despite its well characterized specificity of expression in transgenic mouse (4), the precise function of OC in bone remodeling remains unclear. The location of OC at the bone-forming surfaces (5) and the increased bone mineralization observed in OC gene knockout mice (6) supports a role of OC in suppression of bone mineralization.Due to its tissue specificity, regulation of OC expression has been studied extensively in bone cells. Many regulatory elements have been identified in the proximal 800-bp region of the promoters. These include OSE1, OSE2 (7), AP-1/VDRE (8), and GRE (9). OSE1 and OSE2 were identified in mouse OC (mOC) promoter and are responsible for its tissue specific activity in osteoblasts. Both of these cis-elements are occupied by osteoblast-specific transcription factors, Osf1 and Runx2, respectively (7, 10). Runx2 belongs to the RUNT domain transcription factor family (11) and it has an indispensable role in osteoblast differentiation, maturation, and bone formation (12). Runx2 was shown to bind the OSE2 site and regulates the mOC promoter in a tissue-spec...

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Alterations in the expression of osteonectin, osteopontin and osteocalcin mRNAs during the development of skeletal tissues in vivo

Cited by 104 publications

References 36 publications

Coxsackievirus and adenovirus receptor (CAR)-positive immature osteoblasts as targets of adenovirus-mediated gene transfer for fracture healing

Coxsackievirus and adenovirus receptor (CAR)-positive immature osteoblasts as targets of adenovirus-mediated gene transfer for fracture healing

Transcriptional regulation of osteopontin gene in vivo by PEBP2αA/CBFA1 and ETS1 in the skeletal tissues

Regulation of Human Osteocalcin Promoter in Hormone-independent Human Prostate Cancer Cells

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