Abstract: Disclosed herein are methods and compositions for identifying morphogen analogs. The preferred methods and compositions relate to the discovery that morphogen upregulation of the mouse type X collagen promoter activity is mediated by a MEF-2 like sequence and requires an adjacent AP-1 sequence. Certain methods rest on the use of test cells comprising DNA defining a morphogen-responsive transcription activating element operatively associated with a reporter gene. Other methods rest on the use of DNAs for measuring morphogen-inducible DNA-binding. In certain preferred embodiments, the methods and DNAs involve an osteogenic protein 1 (OP-1) responsive transcription activating element. Substances that mediate interaction with and/or activate the OP-1 responsive transcription activating element are considered herein likely to be useful for reproducing in vivo effects of morphogens such as OP-1.

Abstract: Disclosed herein are methods and compositions for identifying morphogen analogs. The preferred methods and compositions relate to the discovery that morphogen upregulation of the mouse type X collagen promoter activity is mediated by a MEF-2 like sequence and requires an adjacent AP-1 sequence. Certain methods rest on the use of test cells comprising DNA defining a morphogen-responsive transcription activating element operatively associated with a reporter gene. Other methods rest on the use of DNAs for measuring morphogen-inducible DNA-binding. In certain preferred embodiments, the methods and DNAs involve an osteogenic protein 1 (OP-1) responsive transcription activating element. Substances that mediate interaction with and/or activate the OP-1 responsive transcription activating element are considered herein likely to be useful for reproducing in vivo effects of morphogens such as OP-1.

Abstract: The present invention relates to a method for eliciting a disease modifying effect on an arthritic condition in a mammal which comprises administering to the mammal a therapeutically effective amount of an anti-resorptive compound. The present invention also relates to method for eliciting a disease modifying effect on subchondral bone sclerosis, preventing osteophyte formation or progression and preventing joint destruction in a mammal which comprises administering to the mammal a therapeutically effective amount of an anti-resorptive compound.

Abstract: The present invention provides for methods for treating or preventing an inflammatory disease or condition in a mammalian patient in need of such treatment comprising administering to said patient a cyclooxygenase-2 specific inhibitor in combination with an ?V?3, ?V?5? and/or ?V?6 integrin receptor antagonist in an amount effective to treat or prevent the inflammatory disease or condition. The present invention also provides for pharmaceutical compositions for the treatment or prevention of an inflammatory disease or condition. Further, the invention provides for the manufacture of a medicament useful in the treatment or prevention of an inflammatory disease or condition.

Abstract: The present invention relates to methods for identifying compounds useful as inhibitors of farnesyl diphosphate synthase. More particularly, the compounds so identified are useful for inhibiting bone resorption. The present invention also relates to methods for inhibiting bone resorption in a mammal comprising administering to a mammal in need thereof a therapeutically effective amount of a farnesyl diphosphate synthase inhibitor.

Abstract: The present invention provides for a method for the treatment of alveolar bone loss due to periodontal disease in a subject in need of such treatment comprising administration of a therapeutically effective amount of an &agr;v&bgr;3 integrin receptor antagonist in combination with a therapeutically effective amount of a COX-2 inhibitor. Further, the present invention provides for pharmaceutical compositions useful in the methods of the present invention, as well as a method of manufacture of a medicament useful for treating the alveolar bone loss due to periodontal disease.

Abstract: Compounds of structural formula (I) as herein defined are disclosed as useful in a method for modulating the androgen receptor in a tissue selective manner in a patient in need of such modulation, as well as in a method of agonizing the androgen receptor in a patient, and in particular the method wherein the androgen receptor is antagonized in the prostate of a male patient or in the uterus of a female patient and agonized in bone and/or muscle tissue. These compounds are useful in the treatment of conditions caused by androgen deficiency or which can be ameliorated by androgen administration, including: osteoporosis, periodontal disease, bone fracture, bone damage following bone reconstructive surgery, sarcopenia, frailty, aging skin, male hypogonadism, post-menopausal symptoms in women, atherosclerosis, hypercholesterolemia, hyperlipidemia, aplastic anemia and other hematopoietic disorders, pancreatic cancer, renal cancer, arthritis and joint repair, alone or in combination with other active agents.

Abstract: The present invention relates to methods for inhibiting bone resorption in a mammal comprising administering to a mammal in need thereof a therapeutically effective amount of an EP4 receptor subtype antagonist.

Abstract: Compounds of structural formula (I) as herein defined are disclosed as useful in a method for modulating the androgen receptor in a tissue selective manner in a patient in need of such modulation, as well as in a method of agonizing the androgen receptor in a patient, and in particular the method wherein the androgen receptor is antagonized in the prostate of a male patient or in the uterus of a female patient and agonized in bone and/or muscle tissue. These compounds are useful in the treatment of conditions caused by androgen deficiency or which can be ameliorated by androgen administration, including: osteoporosis, periodontal disease, bone fracture, bone damage following bone reconstructive surgery, sarcopenia, frailty, aging skin, male hypogonadism, post-menopausal symptoms in women, atherosclerosis, hypercholesterolemia, hyperlipidemia, aplastic anemia and other hematopoietic disorders, pancreatic cancer, renal cancer, arthritis and joint repair, alone or in combination with other active agents.

Abstract: The present invention relates to methods for identifying compounds useful as inhibitors of farnesyl diphosphate synthase. More particularly, the compounds so identified are useful for inhibiting bone resorption. The present invention also relates to methods for inhibiting bone resorption in a mammal comprising administering to a mammal in need thereof a therapeutically effective amount of a farnesyl diphosphate synthase inhibitor.

Abstract: The present invention relates to methods of identifying compounds useful as modulators of certain stress responsive kinases. More particularly, the compounds so identified are useful for treating or preventing diseases or conditions that are mediated by, for example, abnormal bone resorption or angiogenesis. These compounds are useful for treating or preventing osteoporosis, and inhibiting vascular restenosis, diabetic retinopathy, macular degeneration, angiogenesis, atherosclerosis, inflammation, and tumor growth.

Abstract: The present invention relates to methods for inhibiting bone resorption in a mammal comprising administering to a mammal in need thereof a therapeutically effective amount of an EP4 receptor subtype antagonist.

Abstract: The present invention relates to methods for inhibiting bone resorption in a mammal comprising administering to a mammal in need thereof a therapeutically effective amount of an EP4 receptor subtype antagonist.

Abstract: The inhibition of natural bone formation experienced in the prophylaxis and/or treatment of bone resorption disease with a bisphosphonic acid or a pharmaceutically acceptable salt thereof is overcome by the concommitant administration of an agent that binds to the androgen receptor.

Abstract: The present invention provides for methods for treating or preventing an inflammatory disease or condition in a mammalian patient in need of such treatment comprising administering to said patient a cyclooxygenase-2 specific inhibitor in combination with an &agr;V&bgr;3, &agr;V&bgr;5 and/or &agr;V&bgr;6 integrin receptor antagonist in an amount effective to treat or prevent the inflammatory disease or condition. The present invention also provides for pharmaceutical compositions for the treatment or prevention of an inflammatory disease or condition. Further, the invention provides for the manufacture of a medicament useful in the treatment or prevention of an inflammatory disease or condition.

Abstract: The present invention relates to methods for stimulating bone formation in a mammal comprising administering to a mammal in need thereof a therapeutically effective amount of an EP4 receptor subtype agonist.

Abstract: The present invention relates to methods for identifying compounds useful as inhibitors of geranylgeranyl diphosphate synthase. More particularly, the compounds so identified are useful for inhibiting bone resorption. The present invention also relates to methods for inhibiting bone resorption in a mammal comprising administering to a mammal in need thereof a therapeutically effective amount of a geranylgeranyl diphosphate synthase inhibitor.

Abstract: The present invention relates to methods of inhibiting bone resorption comprising administering a therapeutically effective amount of a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor.

Abstract: The present invention relates to methods for inhibiting bone resorption in a mammal comprising administering to a mammal in need thereof a therapeutically effective amount of an EP4 receptor subtype antagonist.

Abstract: The present invention relates to methods of identifying compounds useful as modulators of certain stress responsive kinases. More particularly, the compounds so identified are useful for treating or preventing diseases or conditions that are mediated by, for example, abnormal bone resorption or angiogenesis. These compounds are useful for treating or preventing osteoporosis, and inhibiting vascular restenosis, diabetic retinopathy, macular degeneration, angiogenesis, atherosclerosis, inflammation, and tumor growth.