Phlpp1 Expression in Osteoblasts Plays a Modest Role in Bone Homeostasis.
Phlpp1 Expression in Osteoblasts Plays a Modest Role in Bone Homeostasis.
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先前的研究表明，Phlpp 1缺乏会改变肢体长度和骨量，但涉及的细胞类型和Phlpp 1对这种作用的要求尚不清楚。为了了解Phlpp 1在成骨细胞中的功能，我们将Phlpp 1 floxed小鼠与携带1型胶原（Col1a12.3kb）-Cre的小鼠杂交。来源于Phlpp 1 cKOCol 1a 1的骨髓基质细胞培养物的矿化没有改变，但炎症基因（例如，Ifng、IL 6、Ccl 8）水平和NF-κB受体激活剂配体/骨保护素（RANKL/OPG）比值通过Phlpp 1消融或化学抑制而增强。12周龄小鼠股骨远端和L5椎体的显微计算机断层扫描显示，每总体积的骨体积没有变化，但Phlpp 1 cKOCol 1a 1条件性敲除雌性小鼠的股骨微结构受损。胫骨近端的骨组织形态计量学记录每个骨表面的成骨细胞或破骨细胞数量没有变化，但每个骨表面的破骨细胞表面略有减少。总之，我们的数据表明，1型胶原表达细胞中Phlpp 1的缺失不会显著改变男性或女性峰值骨量的获得，但可能会增强炎症基因表达和RANKL/OPG的比例。未来的研究检查的作用Phlpp 1模型中的先进的年龄，炎症，或骨细胞，以及功能冗余与相关的Phlpp 2亚型是必要的。版权所有© 2023作者。JBMR Plus由Wiley Periodicals LLC代表美国骨与矿物质研究学会出版。我们的数据表明，1型胶原表达细胞中Phlpp 1的缺失不会显著改变男性或女性峰值骨量的获得，但可能会增强炎症基因表达和RANKL/OPG的比率。
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. 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.
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