CHIMERIC C3-LIKE RHO ANTAGONIST BONE THERAPEUTIC
Methods of treating bone disorders in a subject in need thereof by administering to said subject a therapeutically effective amount of a Rho antagonist are disclosed.
1 . A method of modulating Rho GTPase in a bone cell, comprising contacting the bone cell with an amount of a Rho antagonist that modulates Rho GTPase activity.
2 . The method of claim 1 , wherein the Rho antagonist is a C3 polypeptide, a C3-like polypeptide, or a biologically active fragment thereof.
3 . The method of claim 1 , wherein the Rho antagonist is a conjugate comprising a C3 polypeptide, a C3-like polypeptide, or a biologically active fragment thereof.
4 . The method of claim 3 , wherein the conjugate is a fusion protein comprising a C3 polypeptide, a C3-like polypeptide, or a biologically active fragment thereof.
5 . The method of claim 4 , wherein the conjugate comprises the amino acid sequence of SEQ ID NO:1.
6 . The method of claim 1 , wherein the bone cell is a bone remodeling cell.
7 . The method of claim 6 , wherein the bone remodeling cell is an osteoblast or an osteoblast precursor cell.
8 . The method of claim 6 , wherein the bone remodeling cell is an osteoclast or an osteoclast precursor cell.
9 . A method of promoting bone remodeling in a subject, comprising administering to the subject a therapeutically effective amount of a Rho antagonist, thereby promoting bone remodeling in the subject.
10 . The method of claim 9 , wherein the Rho antagonist is a C3 polypeptide, a C3-like polypeptide, or a biologically active fragment thereof.
11 . The method of claim 9 , wherein the Rho antagonist is a conjugate comprising a C3 polypeptide, a C3-like polypeptide, or a biologically active fragment thereof.
12 . The method of claim 11 , wherein the conjugate is a fusion protein comprising a C3 polypeptide, a C3-like polypeptide, or a biologically active fragment thereof.
13 . The method of claim 12 , wherein the conjugate comprises the amino acid sequence of SEQ ID NO:1.
14 . A method of treating a bone injury in a subject, comprising administering to the subject a therapeutically effect amount of a Rho antagonist, thereby treating the bone injury.
15 . The method of claim 14 , wherein the bone injury is a bone fracture.
16 . The method of claim 14 , wherein the bone injury is a spinal injury.
17 . The method of claim 14 , wherein the bone injury is bone loss incident to a metastasizing tumor.
18 . The method of claim 14 , wherein the Rho antagonist is administered locally to the site of the bone injury.
19 . The method of claim 18 , wherein the Rho antagonist comprises the amino acid sequence of SEQ ID NO:1.
20 . The method of claim 19 , wherein the Rho antagonist is administered at a dosage of from about 0.0001 μg/cm 3 tissue to about 100 μg/cm 3 tissue.
21 . The method of claim 18 , wherein the Rho antagonist is administered in a fibrin sealant.
22 . The method of claim 21 , wherein the fibrin sealant is TISSEEL®.
23 . The method of claim 18 , wherein the Rho antagonist is administered directly to bone tissue using a drug eluting device.
24 . A method of stimulating an osteoblast precursor cell to differentiate into an osteoblast, comprising contacting the osteoblast precursor cell with a Rho antagonist, thereby stimulating the differentiation of the precursor cell.
25 . The method of claim 24 , wherein the Rho antagonist is a C3 polypeptide, a C3-like polypeptide, or a biologically active fragment thereof.
26 . The method of claim 24 , wherein the Rho antagonist is a conjugate comprising a C3 polypeptide, a C3-like polypeptide, or a biologically active fragment thereof.
27 . The method of claim 26 , wherein the conjugate is a fusion protein comprising a C3 polypeptide, a C3-like polypeptide, or a biologically active fragment thereof.
28 . The method of claim 27 , wherein the conjugate comprises the amino acid sequence of SEQ ID NO:1.
29 . A method of inhibiting bone resorption in a subject, comprising administering to the subject a Rho antagonist, thereby inhibiting bone resorption.
30 . The method of claim 29 , wherein the Rho antagonist is a C3 polypeptide, a C3-like polypeptide, or a biologically active fragment thereof.
31 . The method of claim 29 , wherein the Rho antagonist is a conjugate comprising a C3 polypeptide, a C3-like polypeptide, or a biologically active fragment thereof.
32 . The method of claim 31 , wherein the conjugate is a fusion protein comprising a C3 polypeptide, a C3-like polypeptide, or a biologically active fragment thereof.
33 . The method of claim 32 , wherein the conjugate comprises the amino acid sequence of SEQ ID NO:1.
34 . A method of treating a bone injury in a subject, comprising:
obtaining osteoblast precursor cells from the subject;
contacting the precursor cells with a Rho antagonist, thereby stimulating the cells to differentiate into osteoblasts; and
implanting the osteoblasts into the subject.
35 . The method of claim 34 , wherein the Rho antagonist is a C3 polypeptide, a C3-like polypeptide, or a biologically active fragment thereof.
36 . The method of claim 34 , wherein the Rho antagonist is a conjugate comprising a C3 polypeptide, a C3-like polypeptide, or a biologically active fragment thereof.
37 . The method of claim 36 , wherein the conjugate is a fusion protein comprising a C3 polypeptide, a C3-like polypeptide, or a biologically active fragment thereof.
38 . The method of claim 37 , wherein the conjugate comprises the amino acid sequence of SEQ ID NO:1.