Prolyl hydroxylase domain proteins regulate bone mass through their expression in osteoblasts

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• 作者：Ke Zhu^a ; Pingping Song^a ; Yumei Lai^a ; Chuanju Liu^b ; ^c ; Guozhi Xiao^a ; ^d ; ^{xiaogz@sustc.edu.cn" class="auth_mail" title="E-mail the corresponding author}
• 关键词：PHD ; prolyl hydroxylase domain proteins ; BMM ; bone marrow monocyte ; MAR ; mineralization apposition rate ; TRAP ; tartrate-resistant acid phosphatase ; MNC ; multinucleated cell ; CFU-F ; colony-forming unit-fibroblast ; CFU-OB ; colony-forming unit-osteoblast ; RANKL ; receptor activator of nuclear factor kappa-B ligand
• 刊名：Gene
• 出版年：2016
• 出版时间：5 December 2016
• 年：2016
• 卷：594
• 期：1
• 页码：125-130
• 全文大小：1188 K

文摘

The roles of prolyl hydroxylase domain proteins (PHDs) in bone are incompletely understood. Here we deleted the expression of genes encoding PHD1, PHD2, and PHD3 in osteoblasts in mice by breeding the floxed Phd1–3 mice with Col1a1-Cre transgenic mice. Results showed that mice lacking PHD1-3 in osteoblasts (Phd1–3_ob −/−) had increased bone mass. Bone parameters such as bone volume/tissue volume (BV/TV), trabecular number (Tb.N), and trabecular thickness (Tb.Th) were increased, while trabecular spacing (Tb.Sp) was decreased in Phd1–3_ob −/− relative to wild-type (WT) femurs. In contrast, loss of PHD1–3 in osteoblasts did not alter cortical thickness (Cort.Th). The mineralization apposition rate (MAR) was increased in Phd1–3_ob −/− bone compared to that of wild-type (WT) bone, demonstrating an enhancement of osteoblast function. Loss of PHD1-3 increased the number of osteoblast progenitors (CFU-OBs) in bone marrow cultures. Interestingly, deleting Phd1–3 genes in osteoblasts increased osteoclast formation in vitro and in bone.