Prolyl hydroxylase domain proteins regulate bone mass through their expression in osteoblasts.
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 (Phd1-3ob-/-) 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 Phd1-3ob-/-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 Phd1-3ob-/-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.
Department of Biochemistry, Rush University Medical Center, Chicago, IL 60612, United States.
Ke
K
Zhu
Department of Biochemistry, Rush University Medical Center, Chicago, IL 60612, United States.
Pingping
P
Song
Department of Biochemistry, Rush University Medical Center, Chicago, IL 60612, United States.
Yumei
Y
Lai
Department of Orthopedic Surgery, New York University School of Medicine, New York, NY 10003, United States; Department of Cell Biology, New York University School of Medicine, New York, NY 10016, United States.
Chuanju
C
Liu
Department of Biochemistry, Rush University Medical Center, Chicago, IL 60612, United States; Department of Biology and Shenzhen Key Laboratory of Cell Microenvironment, Southern University of Science and Technology, Shenzhen 518055, China. Electronic address: xiaogz@sustc.edu.cn.
Guozhi
G
Xiao
D000818:Animals; D002113:Calcification, Physiologic; D017353:Gene Deletion; D015971:Gene Expression Regulation, Enzymologic; D064799:Hypoxia-Inducible Factor-Proline Dioxygenases / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D009929:Organ Size; D010006:Osteoblasts / Q000201:enzymology* / Q000473:pathology; D010010:Osteoclasts / Q000201:enzymology / Q000473:pathology; D011393:Procollagen-Proline Dioxygenase / Q000096:biosynthesis* / Q000235:genetics
C522721:PHD1 protein, mouse; C522722:PHD3 protein, mouse; D011393:Procollagen-Proline Dioxygenase; C490189:Egln1 protein, mouse; D064799:Hypoxia-Inducible Factor-Proline Dioxygenases
Bone formation; Bone resorption; Osteoblast; Osteoclast; PHD