PDGF-BB secreted by preosteoclasts induces angiogenesis during coupling with osteogenesis

Hui Xie; Zhuang Cui; Long Wang; Zhuying Xia; Yin Hu; Lingling Xian; Changjun Li; Liang Xie; Janet Crane; Mei Wan; Gehua Zhen; Qin Bian; Bin Yu; Weizhong Chang; Tao Qiu; Maureen Pickarski; Le Thi Duong; Jolene J. Windle; Xianghang Luo; Eryuan Liao; X. Cao

doi:10.1038/nm.3668

PDGF-BB secreted by preosteoclasts induces angiogenesis during coupling with osteogenesis

Hui Xie, Zhuang Cui, Long Wang, Zhuying Xia, Yin Hu, Lingling Xian, Changjun Li, Liang Xie, Janet Crane, Mei Wan, Gehua Zhen, Qin Bian, Bin Yu, Weizhong Chang, Tao Qiu, Maureen Pickarski, Le Thi Duong, Jolene J. Windle, Xianghang Luo, Eryuan LiaoX. Cao

School of Medicine

Research output: Contribution to journal › Article › peer-review

324 Scopus citations

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^hiEmcn^hi), couples angiogenesis and osteogenesis. Here, we found that platelet-derived growth factor-BB (PDGF-BB) secreted by preosteoclasts induces CD31^hiEmcn^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^hiEmcn^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^hiEmcn^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^hiEmcn^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.

Original language	English (US)
Pages (from-to)	1270-1278
Number of pages	9
Journal	Nature medicine
Volume	20
Issue number	11
DOIs	https://doi.org/10.1038/nm.3668
State	Published - 2014

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)

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Xie, H., Cui, Z., Wang, L., Xia, Z., Hu, Y., Xian, L., Li, C., Xie, L., Crane, J., Wan, M., Zhen, G., Bian, Q., Yu, B., Chang, W., Qiu, T., Pickarski, M., Duong, L. T., Windle, J. J., Luo, X., ... Cao, X. (2014). PDGF-BB secreted by preosteoclasts induces angiogenesis during coupling with osteogenesis. Nature medicine, 20(11), 1270-1278. https://doi.org/10.1038/nm.3668

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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 (CD31hiEmcnhi), couples angiogenesis and osteogenesis. Here, we found that platelet-derived growth factor-BB (PDGF-BB) secreted by preosteoclasts induces CD31hiEmcnhi 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 CD31hiEmcnhi 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 CD31hiEmcnhi 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 CD31hiEmcnhi 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.",

author = "Hui Xie and Zhuang Cui and Long Wang and Zhuying Xia and Yin Hu and Lingling Xian and Changjun Li and Liang Xie and Janet Crane and Mei Wan and Gehua Zhen and Qin Bian and Bin Yu and Weizhong Chang and Tao Qiu and Maureen Pickarski and Duong, {Le Thi} and Windle, {Jolene J.} and Xianghang Luo and Eryuan Liao and X. Cao",

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AU - Xie, Hui

AU - Cui, Zhuang

AU - Wang, Long

AU - Xia, Zhuying

AU - Hu, Yin

AU - Xian, Lingling

AU - Li, Changjun

AU - Xie, Liang

AU - Crane, Janet

AU - Wan, Mei

AU - Zhen, Gehua

AU - Bian, Qin

AU - Yu, Bin

AU - Chang, Weizhong

AU - Qiu, Tao

AU - Pickarski, Maureen

AU - Duong, Le Thi

AU - Windle, Jolene J.

AU - Luo, Xianghang

AU - Liao, Eryuan

AU - Cao, X.

PY - 2014

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N2 - 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 (CD31hiEmcnhi), couples angiogenesis and osteogenesis. Here, we found that platelet-derived growth factor-BB (PDGF-BB) secreted by preosteoclasts induces CD31hiEmcnhi 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 CD31hiEmcnhi 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 CD31hiEmcnhi 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 CD31hiEmcnhi 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.

AB - 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 (CD31hiEmcnhi), couples angiogenesis and osteogenesis. Here, we found that platelet-derived growth factor-BB (PDGF-BB) secreted by preosteoclasts induces CD31hiEmcnhi 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 CD31hiEmcnhi 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 CD31hiEmcnhi 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 CD31hiEmcnhi 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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PDGF-BB secreted by preosteoclasts induces angiogenesis during coupling with osteogenesis

Abstract

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