Bone increase in rat tibiae by local administration of amino-terminally truncated rhFGF-4(73-206)

Tissue Eng. 2007 Feb;13(2):415-22. doi: 10.1089/ten.2006.0112.

Abstract

Fibroblast growth factor 4 (FGF-4) plays important roles in bone development during embryogenesis. Human FGF-4 consists of 206 amino acid residues. We produced amino-terminally truncated rhFGF-4, named rhFGF-4(73-206), that increases bone mineral density when systemically administered to mice. In the present study, we examined the effects of rhFGF-4(73-206) in bone after local administration. We injected 1 microg of rhFGF-4(73-206) into tibiae of 10-week-old Sprague-Dawley rats. At days 4 and 7, sets of animals were subjected for tibial bone marrow cell culture in an osteogenic medium. The bone marrow cells from FGF-4-injected tibiae produced more alkaline phosphatase-positive cells and mineralized nodules than those from control tibiae, indicating that local injection of rhFGF-4(73-206) increased the osteoblastic population in the bone marrow. The remaining sets of animals were killed on days 7 and 10. The tibiae were then analyzed with soft X-ray, dual energy X-ray absorptiometry, peripheral quantitative computed tomography, and histomorphometry. The radiographic analyses revealed increases in trabecular bone in the tibiae but no difference in the cortical bone between the rhFGF-4(73-206) group and the control group. High bone turnover and a derived increase of trabecular bone mineral density were demonstrated by histomorphometry in the rhFGF-4(73-206) group. The present results indicate that local injection with rhFGF-4(73-206) elicited an increase in the osteogenic cell population in the tibial bone marrow, which resulted in more trabecular bone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / drug effects
  • Bone Marrow Cells / physiology*
  • Calcification, Physiologic / drug effects*
  • Calcification, Physiologic / physiology
  • Cells, Cultured
  • Fibroblast Growth Factor 4 / administration & dosage*
  • Fibroblast Growth Factor 4 / genetics
  • Injections
  • Male
  • Osteogenesis / drug effects*
  • Osteogenesis / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Recombinant Proteins / administration & dosage
  • Tibia / cytology*
  • Tibia / drug effects
  • Tibia / physiology*

Substances

  • FGF4 protein, human
  • Fibroblast Growth Factor 4
  • Recombinant Proteins