Bone increase in rat tibiae by local administration of amino-terminally truncated rhFGF-4(73-206).
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.
Kuroda
Shinji
S
Oral Implantology and Regenerative Dental Medicine, Tokyo Medical and Dental University, Tokyo, Japan. skuroda.mfc@tmd.ac.jp
Kondo
Hisatomo
H
Ohya
Keiichi
K
Kasugai
Shohei
S
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D002113:Calcification, Physiologic / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D051519:Fibroblast Growth Factor 4 / Q000008:administration & dosage* / Q000235:genetics; D007267:Injections; D008297:Male; D010012:Osteogenesis / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000008:administration & dosage; D013977:Tibia / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*
C496445:FGF4 protein, human; D051519:Fibroblast Growth Factor 4; D011994:Recombinant Proteins