Coupling of bone resorption and formation by RANKL reverse signalling
| Autor: | Masashi Honma, Yasutaka Sugamori, Nobuyuki Udagawa, Kazuhiro Aoki, Yoshiaki Kariya, Genki Kato, Hiroshi Suzuki, Masud Khan, Yasuhiko Tabata, Madoka Hayashi, Shigeki Aoki, Yuki Ikebuchi, Josef M. Penninger |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male musculoskeletal diseases Osteoclasts Core Binding Factor Alpha 1 Subunit Bone resorption Bone remodeling 03 medical and health sciences Mice Osteogenesis Osteoclast medicine Animals Bone Resorption Transcription factor Multidisciplinary Osteoblasts Receptor Activator of Nuclear Factor-kappa B biology Activator (genetics) Chemistry Cytoplasmic Vesicles RANK Ligand Cell Differentiation Cell biology Resorption Mice Inbred C57BL RUNX2 030104 developmental biology Cross-Linking Reagents medicine.anatomical_structure Amino Acid Substitution RANKL biology.protein Female Signal transduction Signal Transduction |
| Zdroj: | Yearbook of Paediatric Endocrinology. |
| ISSN: | 1662-4009 |
| DOI: | 10.1530/ey.16.5.17 |
| Popis: | Receptor activator of nuclear factor-kappa B (RANK) ligand (RANKL) binds RANK on the surface of osteoclast precursors to trigger osteoclastogenesis. Recent studies have indicated that osteocytic RANKL has an important role in osteoclastogenesis during bone remodelling; however, the role of osteoblastic RANKL remains unclear. Here we show that vesicular RANK, which is secreted from the maturing osteoclasts, binds osteoblastic RANKL and promotes bone formation by triggering RANKL reverse signalling, which activates Runt-related transcription factor 2 (Runx2). The proline-rich motif in the RANKL cytoplasmic tail is required for reverse signalling, and a RANKL(Pro29Ala) point mutation reduces activation of the reverse signalling pathway. The coupling of bone resorption and formation is disrupted in RANKL(Pro29Ala) mutant mice, indicating that osteoblastic RANKL functions as a coupling signal acceptor that recognizes vesicular RANK. RANKL reverse signalling is therefore a potential pharmacological target for avoiding the reduced bone formation associated with inhibition of osteoclastogenesis. Osteoclasts secrete small extracellular vesicles that stimulate osteoblasts, promoting bone formation via receptor activator of nuclear factor-kappa B ligand (RANKL), thereby linking bone formation and resorption. |
| Databáze: | OpenAIRE |
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