Activin A increases the bone mass of grafted bone in C3H/HeJ mice.
Activin A, a member of the TGF-b superfamily, is abundant in bone matrix, but little is known about its physiological role in bone metabolism. The present study was undertaken to determine whether topical activin A can increase the bone mass of isografted bone. The tibiae were bilaterally dissected from a donor C3H/HeJ mouse and transplanted subcutaneously in the dorsal region of a recipient mouse. One isografted tibia was topically infused for either 1, 2, 3, or 4 weeks with activin A, using an osmotic minipump at a dose of 0.02, 0.2, or 2 ng/hr. The other tibia was infused with 0.9% NaCl (control). The following results were obtained: (1) Topical activin A (2 ng/hr) stimulated periosteal bone formation after 2 or 3 weeks. The bone area in a standardized transverse section averaged 1.3 fold that in the control. (2) Numerous cuboidal or conical osteoblasts appeared on the surface of newly formed bone after the infusion of activin A for 2 or 3 weeks. Autoradiographic studies using 3H-proline revealed that the surface area of newly formed bone labelled with autoradiographic silver grains was greater in activin A-treated bone than in the control, suggesting an increased synthesis and secretion of collagen by osteoblasts. (3) Topical activin A increased the number of osteoclasts after 2 to 4 weeks. Furthermore, enhanced or increased bone resorption was observed in the projected anterior site of activin A-treated bone after 4 weeks. These results suggest that topical activin A increases the bone mass of isografted bone by increasing bone turnover.
Hirotani
H
H
Division of Oral and Maxillofacial Surgery, Department of Oro-Maxillofacial Surgical Science, Tohoku University Graduate School of Dentistry, Seiryo-machi 4-1, Aoba-ku, Sendai, 980-8575, Japan.
Ohtsuka-Isoya
M
M
Mori
S
S
Sakai
R
R
Eto
Y
Y
Echigo
S
S
Shinoda
H
H
D028341:Activins / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D015519:Bone Density / Q000187:drug effects; D001857:Bone Matrix; D016025:Bone Transplantation; D006801:Humans; D028322:Inhibin-beta Subunits / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D010012:Osteogenesis / Q000187:drug effects; D011392:Proline; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000494:pharmacology; D013977:Tibia / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors; D015291:Transforming Growth Factors / Q000008:administration & dosage / Q000494:pharmacology*
D011993:Recombinant Fusion Proteins; C422405:activin A; D028341:Activins; D015291:Transforming Growth Factors; D028322:Inhibin-beta Subunits; D011392:Proline