Local administration of activin promotes fracture healing in the rat fibula fracture model.
Osteogenic activities of activin, a member of the transforming growth factor (TGF)-beta superfamily, have been demonstrated in both in vitro and in vivo studies. The present study investigates the effects of topical application of activin on fracture healing using rat fibula fracture models. Activin (0.4-10 microg/day) was injected locally to the fracture once a day for 2 weeks. Activin promoted callus formation in a dose-dependent manner and both callus volume and callus weight were significantly increased with doses of 2-10 microg/day activin. Also, 3 weeks of activin treatment increased the mechanical strength of the healing bone in addition to the callus mass. Histological study 2 weeks after the fracture revealed that activin promoted endochondral bone formation. Immunohistochemical examination of the fractured tibia revealed that activin was localized to osteoblasts and chondrocytes in the region ossified both endochondrally and intramembranously. These findings suggest that activin expressed during fracture healing promotes the healing process through an autocrine/paracrine mode of action.
Sakai
R
R
Central Research Laboratories, Ajinomoto Co., Inc., Kawasaki, Japan. clk_sakai@te10.ajinomoto.co.jp
Miwa
K
K
Eto
Y
Y
D028341:Activins; D000287:Administration, Topical; D000818:Animals; D001846:Bone Development / Q000187:drug effects; D002146:Bony Callus / Q000187:drug effects / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D005360:Fibula / Q000187:drug effects / Q000293:injuries* / Q000473:pathology; D017102:Fracture Healing / Q000187:drug effects*; D050723:Fractures, Bone / Q000188:drug therapy* / Q000473:pathology; D006133:Growth Substances / Q000032:analysis / Q000494:pharmacology*; D007124:Immunoenzyme Techniques; D007265:Inhibins / Q000032:analysis / Q000494:pharmacology*; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D013314:Stress, Mechanical; D013977:Tibia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013978:Tibial Fractures / Q000378:metabolism / Q000473:pathology; D016474:Weight-Bearing / Q000502:physiology
D006133:Growth Substances; D011994:Recombinant Proteins; D028341:Activins; D007265:Inhibins