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PDGF-BB secreted by preosteoclasts induces angiogenesis during coupling with osteogenesis.
Xie, Hui; Cui, Zhuang; Wang, Long; Xia, Zhuying; Hu, Yin; Xian, Lingling; Li, Changjun; Xie, Liang; Crane, Janet; Wan, Mei; Zhen, Gehua; Bian, Qin; Yu, Bin; Chang, Weizhong; Qiu, Tao; Pickarski, Maureen; Duong, Le Thi; Windle, Jolene J; Luo, Xianghang; Liao, Eryuan; Cao, Xu.
Affiliation
  • Xie H; 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.
  • Cui Z; 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.
  • Wang L; 1] Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. [2] Xiangya Hospital, Central South University, Changsha, Hunan, China.
  • Xia Z; 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.
  • Hu Y; 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.
  • Xian L; Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  • Li C; Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  • Xie L; Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  • Crane J; Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  • Wan M; Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  • Zhen G; Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  • Bian Q; Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  • Yu B; Department of Orthopedics and Trauma, Nan Fang Hospital, Southern Medical University, Guangzhou, Cuangdong, China.
  • Chang W; Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  • Qiu T; Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  • Pickarski M; Bone Biology, Merck Research Laboratories, West Point, Pennsylvania, USA.
  • Duong LT; Bone Biology, Merck Research Laboratories, West Point, Pennsylvania, USA.
  • Windle JJ; Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, Virginia, USA.
  • Luo X; Institute of Endocrinology and Metabolism, Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
  • Liao E; Institute of Endocrinology and Metabolism, Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
  • Cao X; Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Nat Med ; 20(11): 1270-8, 2014 Nov.
Article de En | MEDLINE | ID: mdl-25282358
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.
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Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Ostéoclastes / Ostéogenèse / Néovascularisation physiologique / Protéines proto-oncogènes c-sis Type d'étude: Prognostic_studies Langue: En Journal: Nat Med Sujet du journal: BIOLOGIA MOLECULAR / MEDICINA Année: 2014 Type de document: Article Pays d'affiliation: Chine
Texte intégral
Ajouter à My VHL
Imprimer
XML
PubMed Links
Recherche sur Google

Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Ostéoclastes / Ostéogenèse / Néovascularisation physiologique / Protéines proto-oncogènes c-sis Type d'étude: Prognostic_studies Langue: En Journal: Nat Med Sujet du journal: BIOLOGIA MOLECULAR / MEDICINA Année: 2014 Type de document: Article Pays d'affiliation: Chine