論文 - 詳細
| RRC ID | 43353 |
|---|---|
| 著者 | Ohba S, Kawaguchi H, Kugimiya F, Ogasawara T, Kawamura N, Saito T, Ikeda T, Fujii K, Miyajima T, Kuramochi A, Miyashita T, Oda H, Nakamura K, Takato T, Chung UI. |
| タイトル | Patched1 haploinsufficiency increases adult bone mass and modulates Gli3 repressor activity. |
| ジャーナル | Dev Cell |
| Abstract |
Hedgehog (Hh)-Patched1 (Ptch1) signaling plays essential roles in various developmental processes, but little is known about its role in postnatal homeostasis. Here, we demonstrate regulation of postnatal bone homeostasis by Hh-Ptch1 signaling. Ptch1-deficient (Ptch1+/-) mice and patients with nevoid basal cell carcinoma syndrome showed high bone mass in adults. In culture, Ptch1+/- cells showed accelerated osteoblast differentiation, enhanced responsiveness to the runt-related transcription factor 2 (Runx2), and reduced generation of the repressor form of Gli3 (Gli3rep). Gli3rep inhibited DNA binding by Runx2 in vitro, suggesting a mechanism that could contribute to the bone phenotypes seen in the Ptch1 heterozygotes. Moreover, systemic administration of the Hh signaling inhibitor cyclopamine decreased bone mass in adult mice. These data provide evidence that Hh-Ptch1 signaling plays a crucial role in postnatal bone homeostasis and point to Hh-Ptch1 signaling as a potential molecular target for the treatment of osteoporosis. |
| 巻・号 | 14(5) |
| ページ | 689-99 |
| 公開日 | 2008-5-1 |
| DOI | 10.1016/j.devcel.2008.03.007 |
| PII | S1534-5807(08)00115-9 |
| PMID | 18477452 |
| MeSH | Animals Bone and Bones / diagnostic imaging Bone and Bones / pathology* Cell Differentiation Cells, Cultured Core Binding Factor Alpha 1 Subunit / genetics Core Binding Factor Alpha 1 Subunit / metabolism DNA / metabolism Gene Expression Regulation Haploidy* Hedgehog Proteins / metabolism Humans Kruppel-Like Transcription Factors / genetics Kruppel-Like Transcription Factors / metabolism* Mice Nerve Tissue Proteins / genetics Nerve Tissue Proteins / metabolism* Organ Size Osteoblasts / metabolism Osteoblasts / pathology Patched Receptors Patched-1 Receptor Protein Binding Radiography Receptors, Cell Surface / deficiency* Receptors, Cell Surface / genetics Receptors, Cell Surface / metabolism Repressor Proteins / genetics Repressor Proteins / metabolism* Signal Transduction Stem Cells / metabolism Stem Cells / pathology Transcription, Genetic Zinc Finger Protein Gli3 |
| IF | 10.092 |
| 引用数 | 89 |
| WOS 分野 | DEVELOPMENTAL BIOLOGY CELL BIOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | NIH 3T3 COS-7(RCB0539) 10T1/2(RCB0247) |