Regulation of cell proliferation and differentation using peptides
OwnerMichael F. Holickinventor
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Abstract
Disclosed are methods of inhibiting proliferation and enhancing differentiation of a mammalian cell, inducing proliferation of a mammalian cell, enhancing wound healing, and stimulating hair growth using a peptide which has 10% or greater homology to a region of human parathyroid hormone or human hypercalcemic factor.
Claims52
A method of inhibiting proliferation or enhancing differentiation of a mammalian skin cell, said method comprising contacting a mammalian skin cell in need of inhibited proliferation or enhanced differentiation with a proliferation-inhibiting or differentiation-enhancing amount of a peptide selected from the group consisting of human parathyroid hormone (hPTH), human hypercalcemic factor (hCFF), a hPTH agonist and a hCFF factor agonist,
- wherein said agonist peptides are at least 8 amino acids long, said peptides contain a fragment of 8 amino acids which has at least 4 amino acids in common with the 34 amino acid N-terminal region of hPTH or hCFF, and said peptides are capable of inhibiting proliferation or enhancing the differentiation in vitro of cultured human keratinocytes.
A method of inhibiting proliferation or enhancing differentiation of a mammalian skin cell, said method comprising contacting a mammalian skin cell in need of inhibited proliferation or enhanced differentiation with a proliferation-inhibiting or differentiation-enhancing amount of a peptide selected from the group consisting of hPTH, hCFF, a hPTH agonist and a hCFF agonist,
- wherein said agonist peptides are at least 34 amino acids long, said peptides contain a fragment of 8 amino acids which has at least 4 amino acids in common with the 34 amino acid N-terminal region of hPTH or hCFF, and said peptides are capable of inhabiting proliferation or enhancing the differentiation in vitro of cultured human keratinocytes.
A method of treating a hyperproliferative skin disorder in a mammal, said method comprising contacting a mammalian skin cell in need thereof with an effective amount of a peptide selected from the group consisting of hPTH, hCFF, a hPTH agonist and a hCFF agonist,
- wherein said agonist peptides are at least 8 amino acids long, said peptides contain a fragment of 8 amino acids which has at least 4 amino acids in common with the 34 amino acid N-terminal region of hPTH or hCFF, and said peptides are capable of inhibiting proliferation or enhancing the differentiation in vitro of cultured human keratinocytes.
A method of treating a hyperproliferative skin disorder in a mammal, said method comprising contacting a mammalian skin cell in need thereof with an effective amount of a peptide selected from the group consisting of hPTH, hCFF, a hPTH agonist and a hCFF agonist,
- wherein said agonist peptides are at least 34 amino acids long, said peptides contain a fragment of 8 amino acids which has at least 4 amino acids in common with the 34 amino acid N-terminal region of hPTH or hCFF, and said peptides are capable of inhibiting proliferation or enhancing the differentiation in vitro of cultured human keratinocytes.
A method of inducing proliferation of a mammalian skin cell, said method comprising contacting a mammalian skin cell in need of enhanced proliferation with a proliferation-inducing amount of a peptide selected from the group consisting of a hPTH antagonist and a hCFF antagonist,
- wherein said antagonist peptides are at least 8 amino acids long, said peptides contain a fragment of 8 amino acids which has at least 6 amino acids in common with the 34 amino acid N-terminal region of hPTH or 8 amino acids in common with the 34 amino acid N-terminal region of hCFF, and said peptides are capable of blocking the inhibition of proliferation or stimulation of differentiation in vitro of cultured human keratinocytes by PTH (1-34), 1,25(OH).sub.2 D.sub.3 or CFF (1-34).
A method of inducing proliferation of a mammalian skin cell, said method comprising contacting a mammalian skin cell in need of enhanced proliferation with a proliferation-inducing amount of a peptide selected from the group consisting of a hPTH antagonist and a hCFF antagonist,
- wherein said antagonist peptides are at least 34 amino acids long, said peptides contain a fragment of 8 amino acids which has at least 6 amino acids in common with the 34 amino acid N-terminal region of hPTH or 8 amino acids in common with the 34 amino acid N-terminal region of hCFF, and said peptides are capable of blocking the inhibition of proliferation or stimulation of differentiation in vitro of cultured human keratinocytes by PTH (1-34), 1,25(OH).sub.2 D.sub.3 or CFF (1-34).
A method of enhancing healing of a skin wound in a mammal in need thereof, said method comprising contacting said manual with a wound-healing enhancing amount of a peptide which is a hCFF antagonist,
- wherein said antagonist peptide is at least 8 amino acids long, said peptide contains a fragment of 8 amino acids which has at least 6 amino acids in common with the 34 amino acid N-terminal region of hPTH or 8 amino acids in common with the 34 amino acid N-terminal region of hCFF, and said peptide is capable of enhancing wound healing in an in vivo skin punch assay.
A method of enhancing healing of a skin wound in a mammal in need thereof, said method comprising contacting said mammal with a wound-healing enhancing amount of a peptide selected from the group consisting of a hPTH antagonist and a hCFF antagonist,
- wherein said antagonist peptides are at least 34 amino acids long, said peptides contain a fragment of 8 amino acids which has at least 6 amino acids in common with the 34 amino acid N-terminal region of hPTH or 8 amino acids in common with the 34 amino acid N-terminal region of hCFF, and said peptides are capable of enhancing wound healing in an in vivo skin punch assay.
A method of enhancing or maintaining hair growth in a mammal, said method comprising administering to a mammal in need thereof a peptide selected from the group consisting of a hPTH antagonist and a hCFF antagonist,
- wherein said antagonist peptides are at least 8 amino acids long, said peptides contain a fragment of 8 amino acids which has 8 amino acids in common with the 34 amino acid N-terminal region of hPTH or at least 6 amino acids in common with the 34 amino acid N-terminal region of hCFF, and said peptides are capable of enhancing hair growth in an in vitro hair growth assay.
A method of enhancing or maintaining hair growth in a mammal, said method comprising administering to a mammal in need thereof a peptide selected from the group consisting of a hPTH antagonist and a hCFF antagonist,
- wherein said antagonist peptides are at least 34 amino acids long, said peptides contain a fragment of 8 amino acids which has at least 4 amino acids in common with the 34 amino acid N-terminal region of hPTH or hCFF, and said peptides are capable of enhancing hair growth in an in vitro hair growth assay.
A method of stimulating epidermal regrowth in a mammal in need thereof, said method comprising administering to said mammal a skin growth enhancing amount of a peptide selected from the group consisting of a hPTH antagonist and a hCFF antagonist,
- wherein said antagonist peptides are at least 8 amino acids long, said peptides contain a fragment of 8 amino acids which has at least 6 amino acids in common with the 34 amino acid N-terminal region of hPTH or 8 amino acids in common with the 34 amino acid N-terminal region of hCFF, and said peptides are capable of blocking the inhibition of proliferation or stimulation of differentiation in vitro of cultured human keratinocytes by PTH (1-34), 1,25(OH).sub.2 D.sub.3 or CFF (1-34).
A method of stimulating epidermal regrowth in a mammal in need thereof, said method comprising administering to said mammal a skin growth enhancing amount of a peptide selected from the group consisting of a hPTH antagonist and a hCFF antagonist,
- wherein said antagonist peptides are at least 34 amino acids long, said peptides contain a fragment of 8 amino acids which has at least 6 amino acids in common with the 34 amino acid N-terminal region of hPTH or 8 amino acids in common with the 34 amino acid N-terminal region of hCFF, and said peptides are capable of blocking the inhibition of proliferation or stimulation of differentiation in vitro of cultured human keratinocytes by PTH (1-34), 1,25(OH).sub.2 D.sub.3 or CFF (1-34).
A method of inducing proliferation of a mammalian skin cell, said method comprising contacting a mammalian skin cell in need of enhanced proliferation with a proliferation-inducing amount of a peptide selected from the group consisting of a hPTH antagonist and a hCFF antagonist,
- wherein said antagonist peptides are at least 34 amino acids long, said peptides contain a fragment of 34 amino acids which has at least 17 amino acids in common with the 34 amino acid N-terminal region of hPTH or hCFF, and said peptides are capable of blocking the inhibition of proliferation or stimulation of differentiation in vitro of cultured human keratinocytes by PTH (1-34), 1,25(OH).sub.2 D.sub.3 or CFF (1-34).
A method of enhancing healing of a skin wound in a mammal in need thereof, said method comprising contacting said mammal with a wound-healing enhancing amount of a peptide which is a hCFF antagonist,
- wherein said antagonist peptide is at least 34 amino acids long, said peptide contains a fragment of 34 amino acids which has at least 17 amino acids in common with the 34 amino acid N-terminal region of hPTH or hCFF, and said peptide is capable of enhancing wound healing in an in vivo skin punch assay.
A method of enhancing or maintaining hair growth in a mammal, said method comprising administering to a mammal in need thereof a peptide selected from the group consisting of a hPTH antagonist and a hCFF antagonist,
- wherein said antagonist peptides are at least 3 4 amino acids long, said peptides contain a fragment of 34 amino acids which has at least 17 amino acids in common with the 34 amino acid N-terminal region of hPTH or hCFF, and said peptides are capable of enhancing hair growth in an in vitro hair growth assay.
A method of stimulating epidermal regrowth in a mammal in need thereof, said method comprising administering to said mammal a skin growth enhancing amount of a peptide selected from the group consisting of a hPTH antagonist and a hCFF antagonist,
- wherein said antagonist peptides are at least 34 amino acids long, said peptides contain a fragment of 34 amino acids which has at least 17 amino acids in common with the 34 amino acid N-terminal region of hPTH or hCFF, and said peptides are capable of blocking the inhibition of proliferation or stimulation of differentiation in vitro of cultured human keratinocytes by PTH (1-34), 1,25(OH).sub.2 D.sub.3 or CFF (1-34).
Dependencies are inferred from the claim text.