Charlie Norwood VA Medical Center, Augusta, GA 30904, United States; Institute for Regenerative and Reparative Medicine, Augusta University, 30912, United States; Department of Physiology, Augusta University, 30912, United States; Department of Orthopaedic Surgery, Augusta University, 30912, United States; Department of Medicine, Augusta University, 30912, United States; Department of Oral Biology, Augusta University, 30912, United States; Department of Cellular Biology and Anatomy, Augusta University, 30912, United States.
Charlie Norwood VA Medical Center, Augusta, GA 30904, United States; Department of Physiology, Augusta University, 30912, United States.
Mol Cell Endocrinol. 2018 Feb 5;461:22-31. doi: 10.1016/j.mce.2017.08.005. Epub 2017 Aug 12.
Protein kinase D1 (PRKD1) is thought to play a role in a number of cellular functions, including proliferation and differentiation. We hypothesized that PRKD1 in bone marrow-derived mesenchymal stem cells (BMMSC) could modulate osteogenesis. In BMMSCs from floxed PRKD1 mice, PRKD1 ablation with adenovirus-mediated Cre-recombinase expression inhibited BMMSC differentiation in vitro. In 3- and 6-month-old conditional knockout mice (cKO), in which PRKD1 was ablated in osteoprogenitor cells by osterix promoter-driven Cre-recombinase, bone mineral density (BMD) was significantly reduced compared with floxed control littermates. Microcomputed tomography analysis also demonstrated a decrease in trabecular thickness and bone volume fraction in cKO mice at these ages. Dynamic bone histomorphometry suggested a mineralization defect in the cKO mice. However, by 9 months of age, the bone appeared to compensate for the lack of PRKD1, and BMD was not different. Taken together, these results suggest a potentially important role for PRKD1 in bone formation.
蛋白激酶 D1（PRKD1）被认为在许多细胞功能中发挥作用，包括增殖和分化。我们假设骨髓间充质干细胞（BMMSC）中的 PRKD1 可以调节成骨作用。在 floxed PRKD1 小鼠的 BMMSCs 中，用腺病毒介导的 Cre 重组酶表达进行 PRKD1 缺失会抑制 BMMSC 的体外分化。在 3 个月和 6 个月大的条件性敲除小鼠（cKO）中，用骨钙素启动子驱动的 Cre 重组酶在成骨前体细胞中缺失 PRKD1，与 floxed 对照同窝仔相比，骨密度（BMD）显著降低。微计算机断层扫描分析还表明，这些年龄的 cKO 小鼠的小梁厚度和骨体积分数减少。动态骨组织形态计量学表明 cKO 小鼠存在矿化缺陷。然而，到 9 个月大时，骨骼似乎弥补了 PRKD1 的缺乏，BMD 没有差异。综上所述，这些结果表明 PRKD1 在骨形成中可能具有重要作用。
