Phlpp1 Expression in Osteoblasts Plays a Modest Role in Bone Homeostasis.

Autor: Karkache IY; Department of Orthopedics University of Minnesota Minneapolis MN USA.; College of Veterinary Sciences University of Minnesota Minneapolis MN USA., Molstad DH; Department of Orthopedics University of Minnesota Minneapolis MN USA., Vu E; Department of Orthopedics University of Minnesota Minneapolis MN USA., Jensen ED; School of Dentistry Minneapolis MN USA., Bradley EW; Department of Orthopedics University of Minnesota Minneapolis MN USA.; College of Veterinary Sciences University of Minnesota Minneapolis MN USA.; Department of Orthopedic Surgery Stem Cell Institute, University of Minnesota Minneapolis MN USA.
Jazyk: angličtina
Zdroj: JBMR plus [JBMR Plus] 2023 Aug 28; Vol. 7 (12), pp. e10806. Date of Electronic Publication: 2023 Aug 28 (Print Publication: 2023).
DOI: 10.1002/jbm4.10806
Abstrakt: 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 (Col1a1 2.3kb )-Cre. Mineralization of bone marrow stromal cell cultures derived from Phlpp1 cKO Col1a1 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 L 5 vertebral body of 12-week-old mice revealed no alteration in bone volume per total volume, but compromised femoral bone microarchitecture within Phlpp1 cKO Col1a1 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.
(© 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.)
Databáze: MEDLINE
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