Abstract: Provided herein are methods and devices for inducing the formation of functional replacement nonarticular cartilage tissues and ligament tissues. These methods and devices involve the use of osteogenic proteins, and are useful in repairing defects in the larynx, trachea, interarticular menisci, intervertebral discs, ear, nose, ribs and other fibrocartilaginous tissues in a mammal.

Abstract: The invention disclosed herein provides methods and compositions for the computer-assisted design of morphogen analogs. Practice of the invention is enabled by the use of at least a portion of the atomic co-ordinates defining the three-dimensional structure of human osteogenic protein-1 (hOP-1) as a starting point in the design of the morphogen analogs. In addition, the invention provides methods for producing morphogen analogs of interest, and methods for testing whether the resulting analogs mimic or agonize human OP-1-like biological activity. The invention also provides a family of morphogen analogs produced by such methods.

Abstract: The invention provides methods for alleviating immune cell mediated inflammatory responses to injury to mammalian tissue. The present methods make use of osteogenic protein 1(OP-1), which is appreciated herein as tissue morphogen, i.e., a substance competent to induce tissue-specific morphogenesis of mammalian body tissues in addition to bone and/or cartilage. Alternatively, the present methods make use of other naturally-occurring or biosynthetic proteins sharing a defined structural and functional relationship with OP-1 and thus appreciated herein also to be tissue morphogens. The invention is particularly adapted to alleviating tissue damage associated with ischemia-reperfusion injury or hyperoxia injury in mammals, including humans.

Abstract: Disclosed herein are methods and compositions for identifying morphogen analogs. Preferred methods rest on the use of test cells comprising DNA defining a morphogen-responsive transcription activating element operatively associated with a reporter gene. In certain embodiments, the methods involve an osteogenic protein 1 (OP-1) responsive transcription activating element. Substances that 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 required 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 are (1) nucleic acid sequences, amino acid sequences, homologies, structural features and various other data characterizing a morphogen cell surface receptor; (2) methods for producing receptor proteins, including fragments thereof, using recombinant DNA technology; (3) methods for identifying novel morphogen receptors and their encoding DNAs; (4) methods for identifying compounds capable of modulating endogenous morphogen receptor levels; and (5) methods for identifying morphogen receptor binding analogs useful in the design of morphogen agonists and antagonists for therapeutic, diagnostic and experimental uses.

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 is directed to methods and compositions for alleviating tissue destructive effects associated with the inflammatory response to tissue injury in a mammal. The methods and compositions include administering a therapeutically effective concentration of a morphogen or morphogen-stimulating agent sufficient to alleviate immune cell-mediated tissue destruction.

Abstract: Disclosed are methods and compositions for screening compounds for their ability to modulate expression of a tissue morphogenetic protein, particularly OP-1, OP-1 homologs and closely related proteins, using one or more OP-1-specific, noncoding nucleotide sequences and a suitable reporter gene.

Abstract: Disclosed are methods and compositions useful in dietary applications and capable of enhancing tissue morphogenesis, including tissue development and viability in a mammal, particularly a human. The methods and compositions include a morphogen which, when provided to an individual as a food formulation or supplement, is capable of enhancing tissue development and viability in the individual.

Abstract: Disclosed is a method of screening candidate compounds for the ability to modulate the level of morphogenic protein in mammalian system. The method includes determining a parameter indicative of the level of production of a morphogenic in a cell culture known to produce the morphogen, incubating a candidate compound with the culture for a time sufficient to allow the compound to affect the production of the morphogenic protein, and then assaying the culture again to detect a change in the level of morphogenic protein production.

Abstract: Disclosed are methods and compositions for maintaining the integrity of the gastrointestinal tract luminal lining in a mammal, including (1) limiting epithelial cell proliferation, (2) inhibiting ulcerative lesion formation, (3) inhibiting inflammation normally associated with ulcerative diseases, and (4) stimulating the repair of ulcerative lesions and the regeneration of the luminal tissue. The methods and compositions include a therapeutically effective amount of a morphogen as defined herein.

Abstract: Disclosed are (1) nucleic acid sequences, amino acid sequences, homologies, structural features, and various other data characterizing morphogen cell surface receptors, particularly OP-1-binding cell surface receptors, e.g., ALK-1; (2) methods for producing receptor proteins, including fragments thereof, using recombinant DNA technology; (3) methods for identifying novel morphogen receptors and their encoding DNAs; (4) methods for identifying compounds capable of modulating endogenous morphogen receptor levels; and (5) methods and compositions for identifying and producing morphogen analogs useful in the design of morphogen agonists and antagonists for therapeutic, diagnostic, and experimental uses.

Abstract: Disclosed herein are methods and compositions for identifying morphogen analogs. Preferred methods rest on the use of test cells comprising DNA defining a morphogen-responsive transcription activating element operatively associated with a reporter gene. In certain embodiments, the methods involve an osteogenic protein 1 (OP-1) responsive transcription activating element. Substances that 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: A novel gene, DD-10, and its encoded polypeptide chain, DD-10, expressed during early onset of morphogen-induced mammalian tissue morphogenesis, now has been discovered. Accordingly, the invention identifies a new gene which is a novel biological marker of cell differentiation and tissue morphogenesis, particularly of chondroblast or osteoblast cell differentiation and bone tissue morphogenesis. Disclosed are: (a) methods and compositions for screening for and producing morphogen analogs; (b) novel morphogen analogs; (c) downstream inducers of morphogenesis; (d) a novel marker for evaluating morphogen or morphogen analog dosing; and (e) therapeutic methods and compositions using these analogs and/or downstream inducers.

Abstract: Disclosed are matrices, devices and methods for the manufacture of live autogenous skeletal replacement parts comprising plural different tissues.

Abstract: Disclosed are (1) nucleic acid sequences, amino acid sequences, homologies, structural features and various other data characterizing a morphogen cell surface receptors particularey OP-1-binding cell surface receptors; (2) methods for producing receptor proteins, including fragments thereof, using recombinant DNA technology; (3) methods for identifying novel morphogen receptors and their encoding DNAs; (4) methods and compositions for identifying compounds capable of modulating endogenous morphogen receptor levels; and (5) methods and compositions for identifying morphogen receptor binding analogs useful in the design of morphogen agonists and antagonists for therapeutic, diagnostic and experimental uses.

Abstract: Disclosed are (1) nucleic acid sequences, amino acid sequences, homologies, structural features and various other data characterizing a morphogen cell surface receptor; (2) methods for producing receptor proteins, including fragments thereof, using recombinant DNA technology; (3) methods for identifying novel morphogen receptors and their encoding DNAs; (4) methods for identifying compounds capable of modulating endogenous morphogen receptor levels; and (5) methods for identifying morphogen receptor binding analogs useful in the design of morphogen agonists and antagonists for therapeutic, diagnostic and experimental uses.

Abstract: Disclosed are (1) nucleic acid and amino acid sequences for a novel morphogenic protein; (2) methods for producing and expressing the protein in a biologically active form; and (3) methods for utilizing the protein to induce tissue morphogenesis in a mammal, including methods for increasing a progenitor cell population in a mammal, methods for stimulating progenitor cells to differentiate and maintain their differentiated phenotype in vivo or in vitro, methods for inducing tissue-specific growth in vivo and methods for the replacement of diseased or damaged tissue in vivo.

Abstract: Disclosed are therapeutic treatment methods, compositions and devices for maintaining liver function in a mammal, including methods, compositions and devices for regenerating lost or damaged hepatic tisse, enhancing viability and integration of hepatic tissue and organ transplants, and correcting liver function deficiencies. The methods, compositions and devices on this invention all provide a therapeutically effective morphogen concentration to the hepatic cells to be treated.