Phlpp1 Expression in Osteoblasts Plays a Modest Role in Bone Homeostasis
ABSTRACT Prior work demonstrated that Phlpp1 deficiency alters limb length and bone mass, but the cell types involved and requirement of Phlpp1 for this effect were unclear. To understand the function of Phlpp1 within bone‐forming osteoblasts, we crossed Phlpp1 floxed mice with mice harboring type 1...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-12-01
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| Series: | JBMR Plus |
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| Online Access: | https://doi.org/10.1002/jbm4.10806 |
| _version_ | 1797384936376762368 |
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| author | Ismael Y Karkache David HH Molstad Elizabeth Vu Eric D Jensen Elizabeth W Bradley |
| author_facet | Ismael Y Karkache David HH Molstad Elizabeth Vu Eric D Jensen Elizabeth W Bradley |
| author_sort | Ismael Y Karkache |
| collection | DOAJ |
| description | ABSTRACT Prior work demonstrated that Phlpp1 deficiency alters limb length and bone mass, but the cell types involved and requirement of Phlpp1 for this effect were unclear. To understand the function of Phlpp1 within bone‐forming osteoblasts, we crossed Phlpp1 floxed mice with mice harboring type 1 collagen (Col1a12.3kb)‐Cre. Mineralization of bone marrow stromal cell cultures derived from Phlpp1 cKOCol1a1 was unchanged, but levels of inflammatory genes (eg, Ifng, Il6, Ccl8) and receptor activator of NF‐κB ligand/osteoprotegerin (RANKL/OPG) ratios were enhanced by either Phlpp1 ablation or chemical inhibition. Micro‐computed tomography of the distal femur and L5 vertebral body of 12‐week‐old mice revealed no alteration in bone volume per total volume, but compromised femoral bone microarchitecture within Phlpp1 cKOCol1a1 conditional knockout females. Bone histomorphometry of the proximal tibia documented no changes in osteoblast or osteoclast number per bone surface but slight reductions in osteoclast surface per bone surface. Overall, our data show that deletion of Phlpp1 in type 1 collagen–expressing cells does not significantly alter attainment of peak bone mass of either males or females, but may enhance inflammatory gene expression and the ratio of RANKL/OPG. Future studies examining the role of Phlpp1 within models of advanced age, inflammation, or osteocytes, as well as functional redundancy with the related Phlpp2 isoform are warranted. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research. |
| first_indexed | 2024-03-08T21:46:53Z |
| format | Article |
| id | doaj.art-34133360d66241849078011d4e521091 |
| institution | Directory Open Access Journal |
| issn | 2473-4039 |
| language | English |
| last_indexed | 2024-03-08T21:46:53Z |
| publishDate | 2023-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | JBMR Plus |
| spelling | doaj.art-34133360d66241849078011d4e5210912023-12-20T07:51:27ZengWileyJBMR Plus2473-40392023-12-01712n/an/a10.1002/jbm4.10806Phlpp1 Expression in Osteoblasts Plays a Modest Role in Bone HomeostasisIsmael Y Karkache0David HH Molstad1Elizabeth Vu2Eric D Jensen3Elizabeth W Bradley4Department of Orthopedics University of Minnesota Minneapolis MN USADepartment of Orthopedics University of Minnesota Minneapolis MN USADepartment of Orthopedics University of Minnesota Minneapolis MN USASchool of Dentistry Minneapolis MN USADepartment of Orthopedics University of Minnesota Minneapolis MN USAABSTRACT Prior work demonstrated that Phlpp1 deficiency alters limb length and bone mass, but the cell types involved and requirement of Phlpp1 for this effect were unclear. To understand the function of Phlpp1 within bone‐forming osteoblasts, we crossed Phlpp1 floxed mice with mice harboring type 1 collagen (Col1a12.3kb)‐Cre. Mineralization of bone marrow stromal cell cultures derived from Phlpp1 cKOCol1a1 was unchanged, but levels of inflammatory genes (eg, Ifng, Il6, Ccl8) and receptor activator of NF‐κB ligand/osteoprotegerin (RANKL/OPG) ratios were enhanced by either Phlpp1 ablation or chemical inhibition. Micro‐computed tomography of the distal femur and L5 vertebral body of 12‐week‐old mice revealed no alteration in bone volume per total volume, but compromised femoral bone microarchitecture within Phlpp1 cKOCol1a1 conditional knockout females. Bone histomorphometry of the proximal tibia documented no changes in osteoblast or osteoclast number per bone surface but slight reductions in osteoclast surface per bone surface. Overall, our data show that deletion of Phlpp1 in type 1 collagen–expressing cells does not significantly alter attainment of peak bone mass of either males or females, but may enhance inflammatory gene expression and the ratio of RANKL/OPG. Future studies examining the role of Phlpp1 within models of advanced age, inflammation, or osteocytes, as well as functional redundancy with the related Phlpp2 isoform are warranted. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.https://doi.org/10.1002/jbm4.10806BONE MODELING AND REMODELINGCELLS OF BONEMOLECULAR PATHWAYS—REMODELINGOSTEOCLASTS |
| spellingShingle | Ismael Y Karkache David HH Molstad Elizabeth Vu Eric D Jensen Elizabeth W Bradley Phlpp1 Expression in Osteoblasts Plays a Modest Role in Bone Homeostasis JBMR Plus BONE MODELING AND REMODELING CELLS OF BONE MOLECULAR PATHWAYS—REMODELING OSTEOCLASTS |
| title | Phlpp1 Expression in Osteoblasts Plays a Modest Role in Bone Homeostasis |
| title_full | Phlpp1 Expression in Osteoblasts Plays a Modest Role in Bone Homeostasis |
| title_fullStr | Phlpp1 Expression in Osteoblasts Plays a Modest Role in Bone Homeostasis |
| title_full_unstemmed | Phlpp1 Expression in Osteoblasts Plays a Modest Role in Bone Homeostasis |
| title_short | Phlpp1 Expression in Osteoblasts Plays a Modest Role in Bone Homeostasis |
| title_sort | phlpp1 expression in osteoblasts plays a modest role in bone homeostasis |
| topic | BONE MODELING AND REMODELING CELLS OF BONE MOLECULAR PATHWAYS—REMODELING OSTEOCLASTS |
| url | https://doi.org/10.1002/jbm4.10806 |
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