Osteoclasts are important for bone angiogenesis

Frank C. Cackowski, Judith L. Anderson, Kenneth D. Patrene, Rushir J. Choksi, Steven D. Shapiro, Jolene J. Windle, Harry C. Blair, G. David Roodman

Research output: Contribution to journalArticle

98 Citations (Scopus)

Abstract

Increased osteoclastogenesis and angiogenesis occur in physiologic and pathologic conditions. However, it is unclear if or how these processes are linked. To test the hypothesis that osteoclasts stimulate angiogenesis, we modulated osteoclast formation in fetal mouse metatarsal explants or in adult mice and determined the effect on angiogenesis. Suppression of osteoclast formation with osteoprotegerin dosedependently inhibited angiogenesis and osteoclastogenesis in metatarsal explants. Conversely, treatment with parathyroid hormone related protein (PTHrP) increased explant angiogenesis, which was completely blocked by osteoprotegerin. Further, treatment of mice with receptor activator of nuclear factor-κB ligand (RANKL) or PTHrP in vivo increased calvarial vessel density and osteoclast number. We next determined whether matrix metalloproteinase-9 (MMP-9), an angiogenic factor predominantly produced by osteoclasts in bone, was important for osteoclast-stimulated angiogenesis. The pro-angiogenic effects of PTHrP or RANKL were absent in metatarsal explants or calvaria in vivo, respectively, from Mmp9 -/- mice, demonstrating the importance of MMP-9 for osteoclast-stimulated angiogenesis. Lack of MMP-9 decreased osteoclast numbers and abrogated angiogenesis in response to PTHrP or RANKL in explants and in vivo but did not decrease osteoclast differentiation in vitro. Thus, MMP-9 modulates osteoclast-stimulated angiogenesis primarily by affecting osteoclasts, most probably by previously reported migratory effects on osteoclasts. These results clearly demonstrate that osteoclasts stimulate angiogenesis in vivo through MMP-9.

Original languageEnglish (US)
Pages (from-to)140-149
Number of pages10
JournalBlood
Volume115
Issue number1
DOIs
StatePublished - Jan 7 2010
Externally publishedYes

Fingerprint

Osteoclasts
Bone
Bone and Bones
Matrix Metalloproteinase 9
Parathyroid Hormone-Related Protein
Metatarsal Bones
Osteoprotegerin
Osteogenesis
Angiogenesis Inducing Agents
Cytoplasmic and Nuclear Receptors
Skull

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Cackowski, F. C., Anderson, J. L., Patrene, K. D., Choksi, R. J., Shapiro, S. D., Windle, J. J., ... Roodman, G. D. (2010). Osteoclasts are important for bone angiogenesis. Blood, 115(1), 140-149. https://doi.org/10.1182/blood-2009-08-237628

Osteoclasts are important for bone angiogenesis. / Cackowski, Frank C.; Anderson, Judith L.; Patrene, Kenneth D.; Choksi, Rushir J.; Shapiro, Steven D.; Windle, Jolene J.; Blair, Harry C.; Roodman, G. David.

In: Blood, Vol. 115, No. 1, 07.01.2010, p. 140-149.

Research output: Contribution to journalArticle

Cackowski, FC, Anderson, JL, Patrene, KD, Choksi, RJ, Shapiro, SD, Windle, JJ, Blair, HC & Roodman, GD 2010, 'Osteoclasts are important for bone angiogenesis', Blood, vol. 115, no. 1, pp. 140-149. https://doi.org/10.1182/blood-2009-08-237628
Cackowski FC, Anderson JL, Patrene KD, Choksi RJ, Shapiro SD, Windle JJ et al. Osteoclasts are important for bone angiogenesis. Blood. 2010 Jan 7;115(1):140-149. https://doi.org/10.1182/blood-2009-08-237628
Cackowski, Frank C. ; Anderson, Judith L. ; Patrene, Kenneth D. ; Choksi, Rushir J. ; Shapiro, Steven D. ; Windle, Jolene J. ; Blair, Harry C. ; Roodman, G. David. / Osteoclasts are important for bone angiogenesis. In: Blood. 2010 ; Vol. 115, No. 1. pp. 140-149.
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