Osteogenesis promoter
View Patent ↗The purpose of the present invention is to provide an osteogenesis promoter for directly promoting osteogenesis by osteoblasts, and an agent for preventing and treating bone disease. The present invention is characterized in that a binding inhibitor substance of semaphorin 4D and plexin B1 is used. For the binding inhibitor substance, suitable examples include anti-semaphorin 4D antibody, anti-plexin B1 antibody, and protein comprising the extracellular domain of plexin B1.
1. A method for treating a bone disease characterized by insufficient osteogenesis or excessive bone resorption, comprising administering to a subject in need of treatment an effective amount of an anti-semaphorin 4D antibody or antigen-binding fragment thereof or an anti-plexin B1 antibody or antigen-binding fragment thereof, wherein the antibody or fragment thereof can inhibit binding of semaphorin 4D and plexin B1.
2. The method of claim 1 , wherein the antibody or fragment thereof is monoclonal.
3. The method of claim 1 , wherein the fragment of the antibody is an F(ab′) 2 fragment, an Fab′ fragment, an Fab fragment, an FIT fragment, a disulphide-linked FV fragment, a single-chain FV (scFV) fragment, or a polymer of one or more of said fragments.
4. The method of claim 1 , wherein the antibody or fragment thereof is a human antibody.
5. The method of claim 1 , wherein the bone disease is bone fracture, bone deficiency, osteoporosis, osteomalacia, osteopenia, lumbar pain, Paget's disease of bone, tonic myelitis, articular rheumatism, deformative arthrosis, or a combination thereof.
6. The method of claim 1 , wherein the antibody or fragment thereof is administered orally, by vascular administration, by intravenous administration, by muscular administration, by hypodermic administration, by transdermal administration, by nasal administration, by transpulmonary administration, or any combination thereof.
7. The method of claim 1 , wherein the subject is a mammal.
8. The method of claim 7 , wherein the subject is a human.
9. A method to identify a candidate active ingredient for an osteogenesis acceleration agent, comprising:
(a) contacting semaphorin 4D and plexin B1 in the presence of the candidate active ingredient;
(b) measuring the degree of binding between semaphorin 4D and plexin B1;
(c) comparing the degree of binding with the candidate active ingredient to the degree of binding between semaphorin 4D and plexin B1 when not in the presence of the candidate active ingredient;
(d) identifying the candidate active ingredient as an osteogenesis acceleration agent when the degree of binding between semaphorin 4D and plexin B1 in the presence of candidate active ingredient is lower than the degree of binding between semaphorin 4D and plexin B1 when not in the presence of the candidate active ingredient.
10. A method for accelerating osteogenesis, comprising contacting osteoblasts with an anti-semaphorin 4D antibody or antigen-binding fragment thereof or an anti-plexin B1 antibody or antigen-binding fragment thereof, wherein the antibody or fragment thereof can inhibit binding of semaphorin 4D and plexin B1.
11. The method of claim 10 , wherein the antibody or fragment thereof is monoclonal.
12. The method of claim 10 , wherein the fragment of the antibody is an F(ab′) 2 fragment, an Fab′ fragment, an Fab fragment, an Fv fragment, a disulphide-linked FV fragment, a single-chain FV (scFV) fragment, or a polymer of one or more of said fragments.
13. The method of claim 10 , wherein the antibody or fragment thereof is a human antibody.
14. The method of claim 10 , wherein the antibody or fragment thereof can inhibit the suppression of differentiation of the osteoblasts.
15. The method of claim 1 , wherein the treatment can prevent a decrease in bone quantity.