Abstract
Characterization of the polypeptides present in bone-inductive protein extracts from bovine bone has led to the cloning of seven regulatory molecules, six of which are distantly related to transforming growth factor beta. The three human bone morphogenetic proteins (BMPs) we describe herein, BMP-5, BMP-6, and BMP-7, show extensive sequence similarity to BMP-2, a molecule that by itself is sufficient to induce de novo bone formation in vivo. The additive or synergistic contribution of these BMP-2-related molecules to the osteogenic activity associated with demineralized bone is strongly implicated by the presence of these growth factors in the most active fractions of highly purified bone extract.
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- Benoit R., Ling N., Esch F. A new prosomatostatin-derived peptide reveals a pattern for prohormone cleavage at monobasic sites. Science. 1987 Nov 20;238(4830):1126–1129. doi: 10.1126/science.2891188. [DOI] [PubMed] [Google Scholar]
- Brunner A. M., Marquardt H., Malacko A. R., Lioubin M. N., Purchio A. F. Site-directed mutagenesis of cysteine residues in the pro region of the transforming growth factor beta 1 precursor. Expression and characterization of mutant proteins. J Biol Chem. 1989 Aug 15;264(23):13660–13664. [PubMed] [Google Scholar]
- Cheifetz S., Bassols A., Stanley K., Ohta M., Greenberger J., Massagué J. Heterodimeric transforming growth factor beta. Biological properties and interaction with three types of cell surface receptors. J Biol Chem. 1988 Aug 5;263(22):10783–10789. [PubMed] [Google Scholar]
- Derynck R., Jarrett J. A., Chen E. Y., Eaton D. H., Bell J. R., Assoian R. K., Roberts A. B., Sporn M. B., Goeddel D. V. Human transforming growth factor-beta complementary DNA sequence and expression in normal and transformed cells. Nature. 1985 Aug 22;316(6030):701–705. doi: 10.1038/316701a0. [DOI] [PubMed] [Google Scholar]
- Derynck R., Lindquist P. B., Lee A., Wen D., Tamm J., Graycar J. L., Rhee L., Mason A. J., Miller D. A., Coffey R. J. A new type of transforming growth factor-beta, TGF-beta 3. EMBO J. 1988 Dec 1;7(12):3737–3743. doi: 10.1002/j.1460-2075.1988.tb03257.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Favaloro J., Treisman R., Kamen R. Transcription maps of polyoma virus-specific RNA: analysis by two-dimensional nuclease S1 gel mapping. Methods Enzymol. 1980;65(1):718–749. doi: 10.1016/s0076-6879(80)65070-8. [DOI] [PubMed] [Google Scholar]
- Gentry L. E., Lioubin M. N., Purchio A. F., Marquardt H. Molecular events in the processing of recombinant type 1 pre-pro-transforming growth factor beta to the mature polypeptide. Mol Cell Biol. 1988 Oct;8(10):4162–4168. doi: 10.1128/mcb.8.10.4162. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ling N., Ueno N., Ying S. Y., Esch F., Shimasaki S., Hotta M., Cuevas P., Guillemin R. Inhibins and activins. Vitam Horm. 1988;44:1–46. doi: 10.1016/s0083-6729(08)60692-5. [DOI] [PubMed] [Google Scholar]
- Luyten F. P., Cunningham N. S., Ma S., Muthukumaran N., Hammonds R. G., Nevins W. B., Woods W. I., Reddi A. H. Purification and partial amino acid sequence of osteogenin, a protein initiating bone differentiation. J Biol Chem. 1989 Aug 15;264(23):13377–13380. [PubMed] [Google Scholar]
- Lyons K. M., Pelton R. W., Hogan B. L. Patterns of expression of murine Vgr-1 and BMP-2a RNA suggest that transforming growth factor-beta-like genes coordinately regulate aspects of embryonic development. Genes Dev. 1989 Nov;3(11):1657–1668. doi: 10.1101/gad.3.11.1657. [DOI] [PubMed] [Google Scholar]
- Lyons K., Graycar J. L., Lee A., Hashmi S., Lindquist P. B., Chen E. Y., Hogan B. L., Derynck R. Vgr-1, a mammalian gene related to Xenopus Vg-1, is a member of the transforming growth factor beta gene superfamily. Proc Natl Acad Sci U S A. 1989 Jun;86(12):4554–4558. doi: 10.1073/pnas.86.12.4554. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Madisen L., Webb N. R., Rose T. M., Marquardt H., Ikeda T., Twardzik D., Seyedin S., Purchio A. F. Transforming growth factor-beta 2: cDNA cloning and sequence analysis. DNA. 1988 Jan-Feb;7(1):1–8. doi: 10.1089/dna.1988.7.1. [DOI] [PubMed] [Google Scholar]
- Mason A. J., Hayflick J. S., Ling N., Esch F., Ueno N., Ying S. Y., Guillemin R., Niall H., Seeburg P. H. Complementary DNA sequences of ovarian follicular fluid inhibin show precursor structure and homology with transforming growth factor-beta. Nature. 1985 Dec 19;318(6047):659–663. doi: 10.1038/318659a0. [DOI] [PubMed] [Google Scholar]
- Mason A. J., Niall H. D., Seeburg P. H. Structure of two human ovarian inhibins. Biochem Biophys Res Commun. 1986 Mar 28;135(3):957–964. doi: 10.1016/0006-291x(86)91021-1. [DOI] [PubMed] [Google Scholar]
- Ozkaynak E., Rueger D. C., Drier E. A., Corbett C., Ridge R. J., Sampath T. K., Oppermann H. OP-1 cDNA encodes an osteogenic protein in the TGF-beta family. EMBO J. 1990 Jul;9(7):2085–2093. doi: 10.1002/j.1460-2075.1990.tb07376.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Padgett R. W., St Johnston R. D., Gelbart W. M. A transcript from a Drosophila pattern gene predicts a protein homologous to the transforming growth factor-beta family. Nature. 1987 Jan 1;325(6099):81–84. doi: 10.1038/325081a0. [DOI] [PubMed] [Google Scholar]
- Panganiban G. E., Rashka K. E., Neitzel M. D., Hoffmann F. M. Biochemical characterization of the Drosophila dpp protein, a member of the transforming growth factor beta family of growth factors. Mol Cell Biol. 1990 Jun;10(6):2669–2677. doi: 10.1128/mcb.10.6.2669. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pepinsky R. B., Sinclair L. K., Chow E. P., Mattaliano R. J., Manganaro T. F., Donahoe P. K., Cate R. L. Proteolytic processing of mullerian inhibiting substance produces a transforming growth factor-beta-like fragment. J Biol Chem. 1988 Dec 15;263(35):18961–18964. [PubMed] [Google Scholar]
- Reddi A. H. Cell biology and biochemistry of endochondral bone development. Coll Relat Res. 1981 Feb;1(2):209–226. doi: 10.1016/s0174-173x(81)80021-0. [DOI] [PubMed] [Google Scholar]
- Roberts A. B., Sporn M. B. Transforming growth factor beta. Adv Cancer Res. 1988;51:107–145. [PubMed] [Google Scholar]
- Sampath T. K., Coughlin J. E., Whetstone R. M., Banach D., Corbett C., Ridge R. J., Ozkaynak E., Oppermann H., Rueger D. C. Bovine osteogenic protein is composed of dimers of OP-1 and BMP-2A, two members of the transforming growth factor-beta superfamily. J Biol Chem. 1990 Aug 5;265(22):13198–13205. [PubMed] [Google Scholar]
- Sampath T. K., Reddi A. H. Homology of bone-inductive proteins from human, monkey, bovine, and rat extracellular matrix. Proc Natl Acad Sci U S A. 1983 Nov;80(21):6591–6595. doi: 10.1073/pnas.80.21.6591. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Toole J. J., Knopf J. L., Wozney J. M., Sultzman L. A., Buecker J. L., Pittman D. D., Kaufman R. J., Brown E., Shoemaker C., Orr E. C. Molecular cloning of a cDNA encoding human antihaemophilic factor. Nature. 1984 Nov 22;312(5992):342–347. doi: 10.1038/312342a0. [DOI] [PubMed] [Google Scholar]
- Urist M. R. Bone: formation by autoinduction. Science. 1965 Nov 12;150(3698):893–899. doi: 10.1126/science.150.3698.893. [DOI] [PubMed] [Google Scholar]
- Urist M. R., Iwata H., Ceccotti P. L., Dorfman R. L., Boyd S. D., McDowell R. M., Chien C. Bone morphogenesis in implants of insoluble bone gelatin. Proc Natl Acad Sci U S A. 1973 Dec;70(12):3511–3515. doi: 10.1073/pnas.70.12.3511. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wakefield L. M., Smith D. M., Broz S., Jackson M., Levinson A. D., Sporn M. B. Recombinant TGF-beta 1 is synthesized as a two-component latent complex that shares some structural features with the native platelet latent TGF-beta 1 complex. Growth Factors. 1989;1(3):203–218. doi: 10.3109/08977198908997997. [DOI] [PubMed] [Google Scholar]
- Wang E. A., Rosen V., Cordes P., Hewick R. M., Kriz M. J., Luxenberg D. P., Sibley B. S., Wozney J. M. Purification and characterization of other distinct bone-inducing factors. Proc Natl Acad Sci U S A. 1988 Dec;85(24):9484–9488. doi: 10.1073/pnas.85.24.9484. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wang E. A., Rosen V., D'Alessandro J. S., Bauduy M., Cordes P., Harada T., Israel D. I., Hewick R. M., Kerns K. M., LaPan P. Recombinant human bone morphogenetic protein induces bone formation. Proc Natl Acad Sci U S A. 1990 Mar;87(6):2220–2224. doi: 10.1073/pnas.87.6.2220. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Weeks D. L., Melton D. A. A maternal mRNA localized to the vegetal hemisphere in Xenopus eggs codes for a growth factor related to TGF-beta. Cell. 1987 Dec 4;51(5):861–867. doi: 10.1016/0092-8674(87)90109-7. [DOI] [PubMed] [Google Scholar]
- Wozney J. M. Bone morphogenetic proteins. Prog Growth Factor Res. 1989;1(4):267–280. doi: 10.1016/0955-2235(89)90015-x. [DOI] [PubMed] [Google Scholar]
- Wozney J. M., Rosen V., Celeste A. J., Mitsock L. M., Whitters M. J., Kriz R. W., Hewick R. M., Wang E. A. Novel regulators of bone formation: molecular clones and activities. Science. 1988 Dec 16;242(4885):1528–1534. doi: 10.1126/science.3201241. [DOI] [PubMed] [Google Scholar]
- Wozney J. M. Using purified protein to clone its gene. Methods Enzymol. 1990;182:738–751. doi: 10.1016/0076-6879(90)82057-9. [DOI] [PubMed] [Google Scholar]