Cortical bone maturation in mice requires SOCS3 suppression of gp130/STAT3 signalling in osteocytes
Bone strength is determined by its dense cortical shell, generated by unknown mechanisms. Here we use the Dmp1Cre:Socs3f/f mouse, with delayed cortical bone consolidation, to characterise cortical maturation and identify control signals. We show that cortical maturation requires a reduction in corti...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2020-05-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/56666 |
| _version_ | 1811236793442369536 |
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| author | Emma C Walker Kim Truong Narelle E McGregor Ingrid J Poulton Tsuyoshi Isojima Jonathan H Gooi T John Martin Natalie A Sims |
| author_facet | Emma C Walker Kim Truong Narelle E McGregor Ingrid J Poulton Tsuyoshi Isojima Jonathan H Gooi T John Martin Natalie A Sims |
| author_sort | Emma C Walker |
| collection | DOAJ |
| description | Bone strength is determined by its dense cortical shell, generated by unknown mechanisms. Here we use the Dmp1Cre:Socs3f/f mouse, with delayed cortical bone consolidation, to characterise cortical maturation and identify control signals. We show that cortical maturation requires a reduction in cortical porosity, and a transition from low to high density bone, which continues even after cortical shape is established. Both processes were delayed in Dmp1Cre:Socs3f/f mice. SOCS3 (suppressor of cytokine signalling 3) inhibits signalling by leptin, G-CSF, and IL-6 family cytokines (gp130). In Dmp1Cre:Socs3f/f bone, STAT3 phosphorylation was prolonged in response to gp130-signalling cytokines, but not G-CSF or leptin. Deletion of gp130 in Dmp1Cre:Socs3f/f mice suppressed STAT3 phosphorylation in osteocytes and osteoclastic resorption within cortical bone, leading to rescue of the corticalisation defect, and restoration of compromised bone strength. We conclude that cortical bone development includes both pore closure and accumulation of high density bone, and that these processes require suppression of gp130-STAT3 signalling in osteocytes. |
| first_indexed | 2024-04-12T12:15:16Z |
| format | Article |
| id | doaj.art-0e2e31dc062d473bb947c073d0b97fe7 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T12:15:16Z |
| publishDate | 2020-05-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-0e2e31dc062d473bb947c073d0b97fe72022-12-22T03:33:27ZengeLife Sciences Publications LtdeLife2050-084X2020-05-01910.7554/eLife.56666Cortical bone maturation in mice requires SOCS3 suppression of gp130/STAT3 signalling in osteocytesEmma C Walker0Kim Truong1Narelle E McGregor2Ingrid J Poulton3Tsuyoshi Isojima4Jonathan H Gooi5T John Martin6Natalie A Sims7https://orcid.org/0000-0003-1421-8468St. Vincent’s Institute of Medical Research, Fitzroy, AustraliaSt. Vincent’s Institute of Medical Research, Fitzroy, Australia; University of Melbourne, Department of Medicine at St. Vincent’s Hospital, Fitzroy, AustraliaSt. Vincent’s Institute of Medical Research, Fitzroy, AustraliaSt. Vincent’s Institute of Medical Research, Fitzroy, AustraliaSt. Vincent’s Institute of Medical Research, Fitzroy, Australia; Department of Pediatrics, Teikyo University School of Medicine, Tokyo, JapanSt. Vincent’s Institute of Medical Research, Fitzroy, Australia; Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, AustraliaSt. Vincent’s Institute of Medical Research, Fitzroy, Australia; University of Melbourne, Department of Medicine at St. Vincent’s Hospital, Fitzroy, AustraliaSt. Vincent’s Institute of Medical Research, Fitzroy, Australia; University of Melbourne, Department of Medicine at St. Vincent’s Hospital, Fitzroy, AustraliaBone strength is determined by its dense cortical shell, generated by unknown mechanisms. Here we use the Dmp1Cre:Socs3f/f mouse, with delayed cortical bone consolidation, to characterise cortical maturation and identify control signals. We show that cortical maturation requires a reduction in cortical porosity, and a transition from low to high density bone, which continues even after cortical shape is established. Both processes were delayed in Dmp1Cre:Socs3f/f mice. SOCS3 (suppressor of cytokine signalling 3) inhibits signalling by leptin, G-CSF, and IL-6 family cytokines (gp130). In Dmp1Cre:Socs3f/f bone, STAT3 phosphorylation was prolonged in response to gp130-signalling cytokines, but not G-CSF or leptin. Deletion of gp130 in Dmp1Cre:Socs3f/f mice suppressed STAT3 phosphorylation in osteocytes and osteoclastic resorption within cortical bone, leading to rescue of the corticalisation defect, and restoration of compromised bone strength. We conclude that cortical bone development includes both pore closure and accumulation of high density bone, and that these processes require suppression of gp130-STAT3 signalling in osteocytes.https://elifesciences.org/articles/56666bonedevelopmentosteocytecytokinecortical bone |
| spellingShingle | Emma C Walker Kim Truong Narelle E McGregor Ingrid J Poulton Tsuyoshi Isojima Jonathan H Gooi T John Martin Natalie A Sims Cortical bone maturation in mice requires SOCS3 suppression of gp130/STAT3 signalling in osteocytes eLife bone development osteocyte cytokine cortical bone |
| title | Cortical bone maturation in mice requires SOCS3 suppression of gp130/STAT3 signalling in osteocytes |
| title_full | Cortical bone maturation in mice requires SOCS3 suppression of gp130/STAT3 signalling in osteocytes |
| title_fullStr | Cortical bone maturation in mice requires SOCS3 suppression of gp130/STAT3 signalling in osteocytes |
| title_full_unstemmed | Cortical bone maturation in mice requires SOCS3 suppression of gp130/STAT3 signalling in osteocytes |
| title_short | Cortical bone maturation in mice requires SOCS3 suppression of gp130/STAT3 signalling in osteocytes |
| title_sort | cortical bone maturation in mice requires socs3 suppression of gp130 stat3 signalling in osteocytes |
| topic | bone development osteocyte cytokine cortical bone |
| url | https://elifesciences.org/articles/56666 |
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