Compositions and methods for affecting osteogenesis
OwnerT. Michael Underhill, Arthur V. Sampaio +1inventors
InventorsT. Michael Underhill, Arthur V. Sampaio, Andrea D. Weston
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Abstract
The invention relates to compositions for promoting and inhibiting osteogenesis and to methods for treating bone abnormalities resulting from injury, toxicity or disease and for ex vivo bone tissue engineering.
Claims72
A pharmaceutical composition for stimulation of osteogenesis, said composition comprising:
- a therapeutically effective amount of an RAR antagonist;
- and
- a pharmaceutically acceptable carrier.
The use of an RAR antagonist in the manufacture of a medicament for the stimulation of osteogenesis.
The use of an RAR antagonist in the manufacture of a medicament for the prevention of vitamin D3 induced apoptosis in osteoblasts.
A method for stimulating osteogenesis in a vertebrate having a metabolic bone disease or a non-metabolic bone disease, the method comprising administering to the vertebrate an effective osteogenesis stimulating amount of an RAR antagonist.
A method for treating bone associated disorders in a subject, comprising administering to the subject cells selected from the group consisting of embryonic stem cells, adult stem cells, osteoblastic cells, preosteoblastic cells, skeletal progenitor cells derived from bone, bone marrow or blood and mixtures thereof, wherein said cells have been treated in vitro with an effective amount of an RAR antagonist.
A method for the ex vivo stimulation of bone mineralization, said method comprising culturing subject cells selected from the group consisting of embryonic stem cells, adult stem cells, osteoblastic cells, preosteoblastic cells and skeletal progenitor cells derived from bone, bone marrow, or blood, with an effective amount of an RAR antagonist;
- and incubating said cells for a time sufficient to allow for the promotion of nodule formation.
A method of producing bone at a bone defect site in vivo, the method comprising:
- implanting into the bone defect site a population of osteoblastic cells or osteoblast progenitor cells which have been cultured in vitro in the presence of a RAR antagonist.
A method for treating a degenerative joint disease characterized by bone degeneration, the method comprising:
- delivering a therapeutically effective amount of a RAR antagonist to a disease site.
A pharmaceutical composition for stimulation of osteogenesis, said composition comprising:
- a therapeutically effective amount of an RAR antisense oligonucleotide, and
- a pharmaceutically acceptable carrier.
A method for treating a metabolic or non metabolic bone disease in a patient, said method comprising administering a therapeutically effective amount of a RAR antagonist composition, wherein said composition comprises a RAR antisense oligonucleotide.
A pharmaceutical composition for inhibiting osteogenesis, said composition comprising a therapeutically effective amount of RAR agonist and a pharmaceutically acceptable carrier therefor.
A method for decreasing diseased bone tissue in a mammal, said method comprising administering a therapeutically effective amount of a RAR agonist to said mammal, wherein said RAR agonist inhibits bone mineralization and stimulates apoptosis of diseased bone tissue.
A method for stimulating apoptosis in osteoblastic cells, said method comprising administering an effective amount of a RAR agonist to said osteoblastic cells.
The use of a RAR agonist in a medicament for the inhibition of osteogenesis.
An implantable prosthetic device for repairing bone-associated orthopedic defects and injuries at sites of skeletal surgery, or anomalities in a vertebrate, the device comprising;
- a prosthetic implant having a surface region implantable adjacent to or within a bone tissue;
- and
- a RAR antagonist composition disposed on the surface region in an amount sufficient to promote enhanced bone mineralization and bone formation on said surface.
A composition for stimulating osteogenesis in vivo, the composition comprising;
- cells selected from the group consisting of embryonic stein cells, adult stem cells, osteoblastic cells, preosteoblastic cells and skeletal progenitor cells derived from bone, bone marrow or blood, wherein said cells have been treated with a therapeutically effective amount of an RAR antagonist;
- and
- a pharmaceutically acceptable carrier.
A composition for inhibiting osteogenesis in vivo the composition comprising
- cells selected from the group consisting of embryonic stern cells, adult stem cells, osteoblastic cells, preosteoblastic cells and skeletal progenitor cells derived from bone, bone marrow or blood, wherein said cells have been treated with a therapeutically effective amount of an RAR agonist, and
- a pharmaceutically acceptable carrier.
A method for ex vivo skeletal tissue engineering, said method comprising
- culturing a population of cells in the presence of a antagonist composition;
- and
- applying said cells to an implantable matrix and further incubating for a time sufficient for the cells to undergo osteogenesis;
- wherein the implantable matrix has bone tissue formation incorporating thereon and therein.
Dependencies are inferred from the claim text.