JAK2-IGF1 axis in osteoclasts regulates postnatal growth in mice
Osteoclasts are specialized cells of the hematopoietic lineage that are responsible for bone resorption and play a critical role in musculoskeletal disease. JAK2 is a key mediator of cytokine and growth factor signaling; however, its role in osteoclasts in vivo has yet to be investigated. To elucida...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Clinical investigation
2021-03-01
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| Series: | JCI Insight |
| Subjects: | |
| Online Access: | https://doi.org/10.1172/jci.insight.137045 |
| _version_ | 1819141093470502912 |
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| author | David W. Dodington Jenalyn L. Yumol Jiaqi Yang Evan Pollock-Tahiri Tharini Sivasubramaniyam Sandra M. Sacco Stephanie A. Schroer Yujin E. Li Helen Le Wendy E. Ward Minna Woo |
| author_facet | David W. Dodington Jenalyn L. Yumol Jiaqi Yang Evan Pollock-Tahiri Tharini Sivasubramaniyam Sandra M. Sacco Stephanie A. Schroer Yujin E. Li Helen Le Wendy E. Ward Minna Woo |
| author_sort | David W. Dodington |
| collection | DOAJ |
| description | Osteoclasts are specialized cells of the hematopoietic lineage that are responsible for bone resorption and play a critical role in musculoskeletal disease. JAK2 is a key mediator of cytokine and growth factor signaling; however, its role in osteoclasts in vivo has yet to be investigated. To elucidate the role of JAK2 in osteoclasts, we generated an osteoclast-specific JAK2–KO (Oc-JAK2–KO) mouse using the Cre/Lox-P system. Oc-JAK2–KO mice demonstrated marked postnatal growth restriction; however, this was not associated with significant changes in bone density, microarchitecture, or strength, indicating that the observed phenotype was not due to alterations in canonical osteoclast function. Interestingly, Oc-JAK2–KO mice had reduced osteoclast-specific expression of IGF1, suggesting a role for osteoclast-derived IGF1 in determination of body size. To directly assess the role of osteoclast-derived IGF1, we generated an osteoclast-specific IGF1–KO mouse, which showed a similar growth-restricted phenotype. Lastly, overexpression of circulating IGF1 by human transgene rescued the growth defects in Oc-JAK2–KO mice, in keeping with a causal role of IGF1 in these models. Together, our data show a potentially novel role for Oc-JAK2 and IGF1 in the determination of body size, which is independent of osteoclast resorptive function. |
| first_indexed | 2024-12-22T11:48:58Z |
| format | Article |
| id | doaj.art-8cd2b35c0a604a699cb3cdc5cfd2cf46 |
| institution | Directory Open Access Journal |
| issn | 2379-3708 |
| language | English |
| last_indexed | 2024-12-22T11:48:58Z |
| publishDate | 2021-03-01 |
| publisher | American Society for Clinical investigation |
| record_format | Article |
| series | JCI Insight |
| spelling | doaj.art-8cd2b35c0a604a699cb3cdc5cfd2cf462022-12-21T18:27:03ZengAmerican Society for Clinical investigationJCI Insight2379-37082021-03-0165JAK2-IGF1 axis in osteoclasts regulates postnatal growth in miceDavid W. DodingtonJenalyn L. YumolJiaqi YangEvan Pollock-TahiriTharini SivasubramaniyamSandra M. SaccoStephanie A. SchroerYujin E. LiHelen LeWendy E. WardMinna WooOsteoclasts are specialized cells of the hematopoietic lineage that are responsible for bone resorption and play a critical role in musculoskeletal disease. JAK2 is a key mediator of cytokine and growth factor signaling; however, its role in osteoclasts in vivo has yet to be investigated. To elucidate the role of JAK2 in osteoclasts, we generated an osteoclast-specific JAK2–KO (Oc-JAK2–KO) mouse using the Cre/Lox-P system. Oc-JAK2–KO mice demonstrated marked postnatal growth restriction; however, this was not associated with significant changes in bone density, microarchitecture, or strength, indicating that the observed phenotype was not due to alterations in canonical osteoclast function. Interestingly, Oc-JAK2–KO mice had reduced osteoclast-specific expression of IGF1, suggesting a role for osteoclast-derived IGF1 in determination of body size. To directly assess the role of osteoclast-derived IGF1, we generated an osteoclast-specific IGF1–KO mouse, which showed a similar growth-restricted phenotype. Lastly, overexpression of circulating IGF1 by human transgene rescued the growth defects in Oc-JAK2–KO mice, in keeping with a causal role of IGF1 in these models. Together, our data show a potentially novel role for Oc-JAK2 and IGF1 in the determination of body size, which is independent of osteoclast resorptive function.https://doi.org/10.1172/jci.insight.137045Bone biologyEndocrinology |
| spellingShingle | David W. Dodington Jenalyn L. Yumol Jiaqi Yang Evan Pollock-Tahiri Tharini Sivasubramaniyam Sandra M. Sacco Stephanie A. Schroer Yujin E. Li Helen Le Wendy E. Ward Minna Woo JAK2-IGF1 axis in osteoclasts regulates postnatal growth in mice JCI Insight Bone biology Endocrinology |
| title | JAK2-IGF1 axis in osteoclasts regulates postnatal growth in mice |
| title_full | JAK2-IGF1 axis in osteoclasts regulates postnatal growth in mice |
| title_fullStr | JAK2-IGF1 axis in osteoclasts regulates postnatal growth in mice |
| title_full_unstemmed | JAK2-IGF1 axis in osteoclasts regulates postnatal growth in mice |
| title_short | JAK2-IGF1 axis in osteoclasts regulates postnatal growth in mice |
| title_sort | jak2 igf1 axis in osteoclasts regulates postnatal growth in mice |
| topic | Bone biology Endocrinology |
| url | https://doi.org/10.1172/jci.insight.137045 |
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