title: PDGF-BB secreted by preosteoclasts induces angiogenesis during coupling with osteogenesis.
abstract: Osteogenesis during bone modeling and remodeling is coupled with angiogenesis. A recent study showed that a specific vessel subtype, strongly positive for CD31 and endomucin (CD31(hi)Emcn(hi)), couples angiogenesis and osteogenesis. Here, we found that platelet-derived growth factor-BB (PDGF-BB) secreted by preosteoclasts induces CD31(hi)Emcn(hi) vessel formation during bone modeling and remodeling. Mice with depletion of PDGF-BB in the tartrate-resistant acid phosphatase-positive cell lineage show significantly lower trabecular and cortical bone mass, serum and bone marrow PDGF-BB concentrations, and fewer CD31(hi)Emcn(hi) vessels compared to wild-type mice. In the ovariectomy (OVX)-induced osteoporotic mouse model, serum and bone marrow levels of PDGF-BB and numbers of CD31(hi)Emcn(hi) vessels are significantly lower compared to sham-operated controls. Treatment with exogenous PDGF-BB or inhibition of cathepsin K to increase the number of preosteoclasts, and thus the endogenous levels of PDGF-BB, increases CD31(hi)Emcn(hi) vessel number and stimulates bone formation in OVX mice. Thus, pharmacotherapies that increase PDGF-BB secretion from preosteoclasts offer a new therapeutic target for treating osteoporosis by promoting angiogenesis and thus bone formation.
authors.affiliation: 1] Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. [2] Institute of Endocrinology and Metabolism, Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Xie
authors.affiliation: 1] Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. [2] Department of Orthopedics and Trauma, Nan Fang Hospital, Southern Medical University, Guangzhou, Cuangdong, China.
authors.forename: Zhuang
authors.initials: Z
authors.lastname: Cui
authors.affiliation: 1] Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. [2] Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Long
authors.initials: L
authors.lastname: Wang
authors.affiliation: 1] Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. [2] Institute of Endocrinology and Metabolism, Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Zhuying
authors.initials: Z
authors.lastname: Xia
authors.affiliation: 1] Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. [2] Institute of Endocrinology and Metabolism, Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Lingling
authors.initials: L
authors.lastname: Xian
authors.affiliation: Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Changjun
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Liang
authors.initials: L
authors.lastname: Xie
authors.affiliation: Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Janet
authors.initials: J
authors.lastname: Crane
authors.affiliation: Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Mei
authors.initials: M
authors.lastname: Wan
authors.affiliation: Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Gehua
authors.initials: G
authors.lastname: Zhen
authors.affiliation: Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Qin
authors.initials: Q
authors.lastname: Bian
authors.affiliation: Department of Orthopedics and Trauma, Nan Fang Hospital, Southern Medical University, Guangzhou, Cuangdong, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Yu
authors.affiliation: Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Weizhong
authors.initials: W
authors.lastname: Chang
authors.affiliation: Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Tao
authors.initials: T
authors.lastname: Qiu
authors.affiliation: Bone Biology, Merck Research Laboratories, West Point, Pennsylvania, USA.
authors.forename: Maureen
authors.initials: M
authors.lastname: Pickarski
authors.affiliation: Bone Biology, Merck Research Laboratories, West Point, Pennsylvania, USA.
authors.forename: Le Thi
authors.initials: LT
authors.lastname: Duong
authors.affiliation: Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, Virginia, USA.
authors.forename: Jolene J
authors.initials: JJ
authors.lastname: Windle
authors.affiliation: Institute of Endocrinology and Metabolism, Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Xianghang
authors.initials: X
authors.lastname: Luo
authors.affiliation: Institute of Endocrinology and Metabolism, Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Eryuan
authors.initials: E
authors.lastname: Liao
authors.affiliation: Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Xu
authors.initials: X
authors.lastname: Cao
mesh_terms: D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D000077214:Becaplermin; D056657:Cathepsin K / Q000037:antagonists & inhibitors / Q000378:metabolism; D002452:Cell Count; D002465:Cell Movement / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005269:Femur / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010010:Osteoclasts / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D010012:Osteogenesis / Q000187:drug effects; D010052:Ovariectomy; D010766:Phosphorylation / Q000187:drug effects; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011480:Protease Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis / Q000378:metabolism*; D000071681:Tartrate-Resistant Acid Phosphatase; D055114:X-Ray Microtomography
chemical_list: D017077:Culture Media, Conditioned; D007527:Isoenzymes; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011480:Protease Inhibitors; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin; D051416:Focal Adhesion Protein-Tyrosine Kinases; D051057:Proto-Oncogene Proteins c-akt; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase; D056657:Cathepsin K; C534132:Ctsk protein, mouse