MicroRNA-200 based approaches for modulating bone formation inhibition and bone regeneration
In certain embodiments, the present invention provides the use of microRNA (miR)-200a and/or miR-200c to inhibit ossification and bone formation. In certain embodiments, the present invention provides the use of miR-200a inhibitor to stimulate bone regeneration.
1. A method of stimulating osteogenic differentiation in a patient in need thereof, comprising administering to the patient a therapeutic composition comprising
(a) miR-200c or a first expression cassette expressing miR-200c, and
(b) a second expression cassette comprising a second promoter operably linked to a plasmid-based miR-200a inhibitor (PMIS-200a);
wherein the therapeutic composition stimulates stimulating osteogenic differentiation in the patient, wherein the therapeutic composition comprises the first expression cassette expressing miR-200c, wherein the miR-200c is operably linked to a first promoter.
2. The method of claim 1 , wherein the first promoter is transiently expressed or is constitutively expressed.
3. The method of claim 1 , wherein the first promoter is a tissue-specific or inducible promoter.
4. A method of stimulating osteogenic differentiation in a patient in need thereof, comprising administering to the patient a therapeutic composition comprising
(a) miR-200c or a first expression cassette expressing miR-200c, and
(b) a second expression cassette comprising a second promoter operably linked to a plasmid-based miR-200a inhibitor (PMIS-200a);
wherein the therapeutic composition stimulates stimulating osteogenic differentiation in the patient, wherein the first expression cassette is contained in a first vector.
5. The method of claim 4 , wherein the first vector is a first plasmid.
6. A method of stimulating osteogenic differentiation in a patient in need thereof, comprising administering to the patient a therapeutic composition comprising
(a) miR-200c or a first expression cassette expressing miR-200c, and
(b) a second expression cassette comprising a second promoter operably linked to a plasmid-based miR-200a inhibitor (PMIS-200a);
wherein the therapeutic composition stimulates stimulating osteogenic differentiation in the patient,
wherein the therapeutic composition comprises the second expression cassette, and
wherein the PMIS-200a is operably linked to a second promoter, wherein the second expression cassette is contained in the first vector.
7. The method of claim 6 , wherein the second expression cassette is contained in a second vector.
8. The method of claim 7 , wherein the second vector is a second plasmid.
9. The method of claim 6 , wherein the second promoter is a tissue-specific or inducible promoter.
10. The method of claim 1 , wherein the osteogenic differentiation bone generates oral, craniofacial, calvarial and/or periodontal bone.
11. The method of claim 1 , wherein the therapeutic composition is contained in biodegradable nanoparticle material.
12. The method of claim 11 , wherein the biodegradable nanoparticle material is polyethylenimine (PEI).
13. The method of claim 11 , wherein the biodegradable nanoparticle material is polylactide-co-glycolide (PLGA).
14. The method of claim 1 , wherein the therapeutic composition is contained in a collagen sponge.
15. The method of claim 1 , wherein the therapeutic composition is administered locally.
16. The method of claim 1 , wherein the therapeutic composition is a sustained release formulation.