Osteopontin facilitates angiogenesis, accumulation of osteoclasts, and resorption in ectopic bone

Endocrinology. 2001 Mar;142(3):1325-32. doi: 10.1210/endo.142.3.8006.


Osteoclastic bone resorption requires a number of complex steps that are under the control of local regulatory molecules. Osteopontin is expressed in osteoclasts and is also present in bone matrix; however, its biological function has not been fully understood. To elucidate the role of osteopontin in the process of osteoclastic bone resorption, we conducted ectopic bone implantation experiments using wild-type and osteopontin knockout mouse. In the wild-type group, bone discs from calvariae implanted ectopically in muscle were resorbed, and their mass was reduced by 25% within 4 weeks. In contrast, the mass of the bone discs from calvariae of osteopontin knockout mice was reduced by only 5% when implanted in osteopontin knockout mice. Histological analyses indicated that the number of osteoclasts associated with the implanted bones was reduced in the osteopontin knockout mice. As osteopontin deficiency does not suppress osteoclastogenesis per se, we further examined vascularization immunohistologically and found that the number of vessels containing CD31-positive endothelial cells around the bone discs implanted in muscle was reduced in the osteopontin knockout mice. Furthermore, sc implantation assays indicated that the length and branching points of the newly formed vasculatures associated with the bone discs were also reduced in the absence of osteopontin. In this assay, tartrate-resistant acid phosphatase-positive area of the bone discs was also reduced in the osteopontin knockout mice, indicating further the link between the osteopontin-dependent vascularization and osteoclast accumulation. The bone resorption defect could be rescued by topical administration of recombinant osteopontin to the bones implanted in muscle. These observations indicate that osteopontin is required for efficient vascularization by the hemangiogenic endothelial cells and subsequent osteoclastic resorption of bones.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Bone Resorption / pathology
  • Bone Resorption / physiopathology*
  • Bone and Bones*
  • Cell Division / physiology
  • Choristoma / physiopathology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout / genetics
  • Muscle, Skeletal
  • Muscular Diseases / physiopathology
  • Neovascularization, Physiologic / physiology*
  • Osteoclasts / drug effects
  • Osteoclasts / pathology*
  • Osteopontin
  • Sialoglycoproteins / genetics
  • Sialoglycoproteins / pharmacology
  • Sialoglycoproteins / physiology*


  • Sialoglycoproteins
  • Spp1 protein, mouse
  • Osteopontin