Dissociation of angiogenesis and osteoclastogenesis during endochondral bone formation in neonatal mice.

Abstract

Invasion of the mineralized matrix by endothelial cells and osteoclasts is a key event in endochondral bone formation. To examine the putative role of osteoclast activity in the angiogenic process, we used two in vivo models of suppressed bone resorption: mice treated with the bisphosphonate clodronate and in osteoclast-deficient, osteopetrotic mice. Angiogenesis was assessed in caudal vertebrae of these neonatal mice. This model enables us to study the interaction between osteoclasts and endothelial cells during endochondral bone formation. In control conditions, sinusoid-like structures were detected in the vicinity of tartrate resistance acid phosphatase positive (TRAcP+) osteoclasts. Treatment with clodronate completely abolished osteoclastic bone resorption, whereas angiogenesis remained unaffected. In line with these observations, in the osteopetrotic mouse mutants c-fos knockout mice and op/op mice, capillaries invaded the calcified cartilage in the absence of osteoclasts. In conclusion, our data strongly suggest that during endochondral bone formation, vascular invasion can occur in the absence of osteo(chondro)clastic resorption. In addition, bisphosphonates show no apparent effect on angiogenesis in this in vivo model. These findings may have important clinical implications in the management of skeletal disorders such as metastatic bone disease, in which both osteoclastic bone resorption and angiogenesis contribute to tumor growth. On the other hand, our results confirm that bisphosphonates can be used safely in the treatment of disorders that affect the growing skeleton, such as in juvenile osteoporosis.

• Authors: Martine M L Deckers, Ermond R Van Beek, Gabri Van Der Pluijm, Antoinette Wetterwald, Lianne Van Der Wee-Pals, Marco G Cecchini, Socrates E Papapoulos, Clemens W G M Löwik
• Journal: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research (J Bone Miner Res) Vol. 17 Issue 6 Pg. 998-1007 (Jun 2002) ISSN: 0884-0431 [Print] United States
• PMID: 12054176 (Publication Type: Journal Article)

Chemical References

• Alkaline Phosphatase

Topics

• Alkaline Phosphatase (metabolism)
• Animals
• Animals, Newborn
• Bone Development
• Bone Resorption
• Endothelium (cytology)
• Immunohistochemistry
• Mice
• Mice, Mutant Strains
• Neovascularization, Physiologic
• Osteoclasts (cytology, enzymology)
• Osteopetrosis (pathology)
• Tail (cytology)