Abstract: The invention relates to compositions and methods for use in treating skeletal system disorders in a vertebrate at risk for bone loss, and in treating conditions that are characterized by the need for bone growth, in treating fractures, and in treating cartilage disorders. More specifically, the invention concerns the use of inhibitors of microtubule assembly for enhancing bone growth.

Abstract: The present invention relates to pharmacologically active compounds which are capable of binding to nuclear hormone receptors and are useful for the stimulation of osteoblast proliferation and ultimately bone growth. This invention also relates to the use of such compounds for the treatment or prevention of diseases and/or disorders associated with nuclear hormone receptor families.

Abstract: The E3 ubiquitin ligases which are specific to ubiquitination of proteins relevant to bone formation are useful targets for protocols or compounds to ameliorate bond disorders. These ligases are &bgr;-TrCP, Smurf1 and Smurf2.

Abstract: The present invention involves the identification and use of compositions for treating myeloma bone disease. The compositions inhibit proteasomal activity and decrease the activity of the transcription factor NF-&kgr;B. Assessment of a candidate compound for its ability to inhibit production or activity of proteasomal enzymes or NF-&kgr;B provides a useful means to identify agents to treat myeloma bone disease.

Abstract: Antagonists of &agr;4 integrin/&agr;4 integrin ligand adhesion, which inhibit the biological effects of such adhesion are described and methods for their use are detailed. Such antagonists are useful in suppressing bone destruction associated with multiple myeloma. The homing of multiple myeloma cells to bone marrow and their &agr;4 integrin-dependent release of bone-resorbing factors, resulting in bone destruction in patients with multiple myeloma, is inhibited.

Abstract: Compounds that inhibit the activity of NF-&kgr;B or inhibit the activity of the proteasome or both promote bone formation and are thus useful in treating osteoporosis, bone fracture or deficiency, primary or secondary hyperparathyroidism, periodontal disease or defect, metastatic bone disease, osteolytic bone disease, post-plastic surgery, post-prosthetic joint surgery, and post-dental implantation.

Abstract: Compounds that inhibit the activity of NF-&kgr;B or inhibit the activity of the proteasome or both promote bone formation and hair growth and are thus useful in treating osteoporosis, bone fracture or deficiency, primary or secondary hyperparathyroidism, periodontal disease or defect, metastatic bone disease, osteolytic bone disease, post-plastic surgery, post-prosthetic joint surgery, and post-dental implantation; they also stimulate the production of hair follicles and are thus useful in stimulating hair growth, including hair density, in subject where this is desirable.

Abstract: Compounds that inhibit the activity of NF-&kgr;B or inhibit the activity of the proteasome or both promote bone formation and hair growth and are thus useful in treating osteoporosis, bone fracture or deficiency, primary or secondary hyperparathyroidism, periodontal disease or defect, metastatic bone disease, osteolytic bone disease, post-plastic surgery, post-prosthetic joint surgery, and post-dental implantation; they also stimulate the production of hair follicles and are thus useful in stimulating hair growth, including hair density, in subject where this is desirable.

Abstract: Compounds containing two aromatic systems covalently linked through a linker containing one or more atoms, or “linker” defined as including a covalent bond per se so as to space the aromatic systems at a distance 1.5-15 Å, are effective in treating conditions associated with bone deficits. The compounds can be administered to vertebrate subjects alone or in combination with additional agents that promote bone growth or that inhibit bone resorption. They can be screened for activity prior to administration by assessing their ability to effect the transcription of a reporter gene coupled to a promoter associated with a bone morphogenetic protein and/or their ability to stimulate calvarial growth in model animal systems.

Abstract: Compounds that inhibit the activity of NF-&kgr;B or inhibit the activity of the proteasome or both promote hair growth and stimulate the production of hair follicles and are thus useful in stimulating hair growth, including hair density, in subject where this is desirable.

Abstract: A food or food supplement which comprises a compound that enhances bone growth in vertebrates is described wherein the food or foodstuff is formulated so as to provide the desired bone growth enhancing effect.

Abstract: A cell-based assay technique for identifying and evaluating chemical compounds and agents which affect the production of PTH-rP in mammalian cells and other cell types is set forth. Specifically, tumor cell lines are transformed with an expression vector comprising a DNA sequence encoding a promoter region of PTH-rP operatively linked to a reporter gene encoding an assayable product and cultured under conditions which permit expression of the assayable product. Chemical agents and factors can then be identified by their ability to modulate the expression of the reporter gene, thereby affecting the production of the assayable product. Such agents are then tested for inhibitory effects on tumor cell growth and for stimulatory effects on bone formation and repair.

Abstract: Various embodiments of statin compounds are shown to enhance the formation of bone and are thus useful in treating osteoporosis, bone fracture or deficiency, primary or secondary hyperparathyroidism, periodontal disease or defect, metastatic bone disease, osteolytic bone disease, post-plastic surgery, post-prosthetic joint surgery, and post-dental implantation.

Abstract: Antagonists of &agr;4 integrin/&agr;4 integrin ligand adhesion, which inhibit the biological effects of such adhesion are described and methods for their use are detailed. Such antagonists are useful in suppressing bone destruction associated with multiple myeloma. The homing of multiple myeloma cells to bone marrow and their &agr;4 integrin-dependent release of bone-resorbing factors, resulting in bone destruction in patients with multiple myeloma, is inhibited.

Abstract: Antagonists of alpha 4 integri/alpha 4 integrin ligand adhesion, which inhibit the biological effects of such adhesion are described and methods for their use are detailed. Such antagonists are eseful in supressing bone destruction associated with multiple myeloma.

Abstract: Compounds containing two aromatic systems covalently linked through a linker containing one or more atoms, or “linker” defined as including a covalent bond per se so as to space the aromatic systems at a distance 1.5-15 Å, are effective in treating conditions associated with bone deficits. The compounds can be administered to vertebrate subjects alone or in combination with additional agents that promote bone growth or that inhibit bone resorption. They can be screened for activity prior to administration by assessing their ability to effect the transcription of a reporter gene coupled to a promoter associated with a bone morphogenetic protein and/or their ability to stimulate calvarial growth in model animal systems.

Abstract: Compounds of the formula 1

Abstract: Compounds containing two aromatic systems covalently linked through a linker containing one or more atoms, or “linker” defined as including a covalent bond per se so 29 as to space the aromatic systems at a distance 1.5-15Å, are effective in treating conditions associated with bone deficits. The compounds can be administered to vertebrate subjects alone or in combination with additional agents that promote bone growth or that inhibit bone resorption. They can be screened for activity prior to administration by assessing their ability to effect the transcription of a reporter gene coupled to a promoter associated with a bone morphogenetic protein and/or their ability to stimulate calvarial growth in model animal systems.

Abstract: Compounds containing two aromatic systems covalently linked through a linker containing one or more atoms, or "linker" defined as including a covalent bond per se so as to space the aromatic systems at a distance 1.5-15 .ANG., are effective in treating conditions associated with bone deficits. The compounds can be administered to vertebrate subjects alone or in combination with additional agents that promote bone growth or that inhibit bone resorption. They can be screened for activity prior to administration by assessing their ability to effect the transcription of a reporter gene coupled to a promoter associated with a bone morphogenetic protein and/or their ability to stimulate calvarial growth in model animal systems.

Abstract: Methods and compositions for identifying osteogenic agents are disclosed, wherein a bone morphogenetic protein promoter is utilized in an assay system to modulate the production of an assayable product of a reporter gene.