Selective inhibitors of the osteoblast proteasome stimulate bone formation in vivo and in vitro

Journal of Clinical Investigation

Volumn 111, Issue 11, 2003, Pages 1771-1782

  Garrett, I R ^a   Chen, D ^a,b   Gutierrez, G ^a   Zhao, M ^a,b   Escobedo, A ^a   Rossini, G ^a   Harris, S E ^c   Gallwitz, W ^a   Kim, K B ^d   Hu, S ^d   Crews, C M ^d   Mundy, G R ^a,b  

^a OsteoScreen   (United States)

^b UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT SAN ANTONIO   (United States)

^c UNIVERSITY OF MISSOURI KANSAS CITY   (United States)

^d YALE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BONE MORPHOGENETIC PROTEIN 2; BONE MORPHOGENETIC PROTEIN 4; EPOXOMICIN; MESSENGER RNA; NOGGIN; PROTEASOME; PROTEASOME INHIBITOR; PROTEASOME INHIBITOR 1; TRANSCRIPTION FACTOR GLI3; UBIQUITIN; UNCLASSIFIED DRUG; BMP2 PROTEIN, HUMAN; BMP2 PROTEIN, MOUSE; BONE MORPHOGENETIC PROTEIN; CARRIER PROTEIN; CYSTEINE PROTEINASE; DNA; LUCIFERASE; MULTIENZYME COMPLEX; NOGGIN PROTEIN; PROTEIN; TRANSFORMING GROWTH FACTOR BETA;

ANIMAL CELL; ANIMAL TISSUE; ARTICLE; BETA CHAIN; CELL DIFFERENTIATION; CONTROLLED STUDY; DROSOPHILA; GENE EXPRESSION; IN VITRO STUDY; IN VIVO STUDY; MOUSE; NONHUMAN; ORGAN CULTURE; OSSIFICATION; OSTEOBLAST; OSTEOLYSIS; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN EXPRESSION; PROTEIN PROCESSING; RODENT; ANIMAL; BONE; BONE DEVELOPMENT; CELL DIVISION; CELL LINE; DOSE RESPONSE; DRUG ANTAGONISM; ENZYME LINKED IMMUNOSORBENT ASSAY; GENE VECTOR; GENETIC TRANSCRIPTION; GENETIC TRANSFECTION; HUMAN; INSTITUTE FOR CANCER RESEARCH MOUSE; METABOLISM; NORTHERN BLOTTING; ORGAN CULTURE TECHNIQUE; PROMOTER REGION; SKULL; WESTERN BLOTTING;

ANIMALS; BLOTTING, NORTHERN; BLOTTING, WESTERN; BONE AND BONES; BONE DEVELOPMENT; BONE MORPHOGENETIC PROTEINS; CARRIER PROTEINS; CELL DIVISION; CELL LINE; CYSTEINE ENDOPEPTIDASES; DNA; DOSE-RESPONSE RELATIONSHIP, DRUG; ENZYME-LINKED IMMUNOSORBENT ASSAY; GENETIC VECTORS; HUMANS; LUCIFERASES; MICE; MICE, INBRED ICR; MULTIENZYME COMPLEXES; ORGAN CULTURE TECHNIQUES; OSTEOBLASTS; PROMOTER REGIONS (GENETICS); PROTEASOME ENDOPEPTIDASE COMPLEX; PROTEINS; RNA, MESSENGER; SKULL; TRANSCRIPTION, GENETIC; TRANSFECTION; TRANSFORMING GROWTH FACTOR BETA;

EID: 0038819051     PISSN: 00219738     EISSN: None     Source Type: Journal    
DOI: 10.1172/JCI16198     Document Type: Article

References (36)

1. Hauschka, P.V., Mavrakos, A.E., Iafrati, M.D., Doleman, S.E., and Klagsbrun, M. 1986. Growth factors in bone matrix. Isolation of multiple types by affinity chromatography on heparin-Sepharose. J. Biol. Chem. 261:12665-12674.
2. Mundy, G.R., et al. 1995. The effects of cytokines and growth factors on osteoblastic cells. Bone. 17(Suppl.):71S-75S.
3. Pfeilschifter, J., and Mundy, G.R. 1987. Modulation of type beta transforming growth factor activity in bone cultures by osteotropic hormones. Proc. Natl. Acad. Sci. U. S. A. 84:2024-2028.
4. Kisselev, A.F., and Goldberg, A.L. 2001. Proteasome inhibitors: from research tools to drug candidates. Chem. Biol. 8:739-758.
5. Goldberg, A.L., Akopian, T.N., Kisselev, A.F., Lee, D.H., and Rohrwild, M. 1997. New insights into the mechanisms and importance of the proteasome in intracellular protein degradation. Biol. Chem. 378:131-140.
6. Goldberg, A.L., Elledge, S.J., and Harper, J.W. 2001. The cellular chamber of doom. Sci. Am. 284:68-73.
7. Sin, N., et al. 1999. Total synthesis of the potent proteasome inhibitor epoxomicin: a useful tool for understanding proteasome biology. Bioorg. Med. Chem. Lett. 9:2283-2288.
8. Sin, N., Meng, L., Auth, H., and Crews, C.M. 1998. Eponemycin analogues: syntheses and use as probes of angiogenesis. Bioorg. Med. Chem. 6:1209-1217.
9. Elofsson, M., Splittgerber, U., Myung, J., Mohan, R., and Crews, C.M. 1999. Towards subunit-specific proteasome inhibitors: synthesis and evaluation of peptide alpha',beta'-epoxyketones. Chem. Biol. 6:811-822.
10. Traianedes, K., Dallas, M.R., Garrett, I.R., Mundy, G.R., and Bonewald, L.F. 1998.5-Lipoxygenase metabolites inhibit bone formation in vitro. Endocrinology. 139:3178-3184.
11. Mundy, G., et al. 1999. Stimulation of bone formation in vitro and in rodents by statins. Science. 286:1946-1949.
12. Dunstan, C.R., et al. 1999. Systemic administration of acidic fibroblast growth factor (FGF-1) prevents bone loss and increases new bone formation in ovariectomized rats. J. Bone Miner. Res. 14:953-959.
13. Ghosh-Choudhury, N., et al. 1996. Immortalized murine osteoblasts derived from BMP 2-T-antigen expressing transgenic mice. Endocrinology. 137:331-339.
14. Rock, K.L., et al. 1994. Inhibitors of the proteasome block the degradation of most cell proteins and the generation of peptides presented on MHC class I molecules. Cell. 78:761-771.
15. Dai, P., et al. 1999. Sonic Hedgehog-induced activation of the Gli1 promoter is mediated by GLI3. J. Biol. Chem. 274:8143-8152.
16. Meng, L., Kwok, B.H., Sin, N., and Crews, C.M. 1999. Eponemycin exerts its antitumor effect through the inhibition of proteasome function. Cancer Res. 59:2798-2801.
17. Palombella, V.J., Rando, O.J., Goldberg, A.L., and Maniatis, T. 1994. The ubiquitin-proteasome pathway is required for processing the NF-kappa B1 precursor protein and the activation of NF-kappa B. Cell. 78:773-785.
18. Samuels, A., Perry, M.J., Gibson, R.L., and Tobias, J.H. 1999. The anabolic actions of estrogen and PTH on the murine skeleton are additive. J. Bone Miner. Res. 14:S452. (Abstr.)
19. Jiang, J., and Struhl, G. 1998. Regulation of the Hedgehog and Wingless signalling pathways by the F-box/WD40-repeat protein Slimb. Nature. 391:493-496.
20. Methot, N., and Basler, K. 1999. Hedgehog controls limb development by regulating the activities of distinct transcriptional activator and repressor forms of Cubitus interruptus. Cell. 96:819-831.
21. Muller, B., and Basler, K. 2000. The repressor and activator forms of Cubitus interruptus control Hedgehog target genes through common generic gli-binding sites. Development. 127:2999-3007.
22. Smith, W.C., and Harland, R.M. 1992. Expression cloning of noggin, a new dorsalizing factor localized to the Spemann organizer in Xenopus embryos. Cell. 70:829-840.
23. Brunet, L.J., McMahon, J.A., McMahon, A.P., and Harland, R.M. 1998. Noggin, cartilage morphogenesis, and joint formation in the mammalian skeleton. Science. 280:1455-1457.
24. Hui, C.C., and Joyner, A.L. 1993. A mouse model of greig cephalopolysyndactyly syndrome: the extra-toesJ mutation contains an intragenic deletion of the Gli3 gene. Nat. Genet. 3:241-246.
25. Harris, S.E., et al. 1994. Expression of bone morphogenetic protein messenger RNA in prolonged cultures of fetal rat calvarial cells. J. Bone Miner. Res. 9:389-394.
26. Rao, S., et al. 1999. Lovastatin-mediated G1 arrest is through inhibition of the proteasome, independent of hydroxymethyl glutaryl-CoA reductase. Proc. Natl. Acad. Sci. U. S. A. 96:7797-7802.
27. Garrett, I.R., et al. 2000. Statins mediate their effects on osteoblasts by inhibition of HMG-CoA reductase and ultimately BMP-2. J. Bone Miner. Res. 15:S225. (Abstr.)
28. Ingham, P.W. 1998. Transducing Hedgehog: the story so far. EMBO J. 17:3505-3511.
29. Chen, C.H., et al. 1999. Nuclear trafficking of Cubitus interruptus in the transcriptional regulation of Hedgehog target gene expression. Cell. 98:305-316.
30. Aza-Blanc, P., Ramirez-Weber, F.A., Lager, M.P., Schwartz, C., and Kornberg, T.B. 1997. Proteolysis that is inhibited by hedgehog targets Cubitus interruptus protein to the nucleus and converts it to a repressor. Cell. 89:1043-1053.
31. Adams, J., et al. 1999. Proteasome inhibitors: a novel class of potent and effective antitumor agents. Cancer Res. 59:2615-2622.
32. Yu, R., Ren, S.G., and Melmed, S. 2002. Proteasome inhibitors induce apoptosis in growth hormone- and prolactin-secreting rat pituitary tumor cells. J. Endocrinol. 174:379-386.
33. Driscoll, J., Brown, M.G., Finley, D., and Monaco, J.J. 1993. MHC-linked LMP gene products specifically alter peptidase activities of the proteasome. Nature. 365:262-264.
34. Fenteany, G., et al. 1995. Inhibition of proteasome activities and subunit-specific amino-terminal threonine modification by lactacystin. Science. 268:726-731.
35. Meng, L., et al. 1999. Epoxomicin, a potent and selective proteasome inhibitor, exhibits in vivo antiinflammatory activity. Proc. Natl. Acad. Sci. U. S. A. 96:10403-10408.
36. Groll, M., Koguchi, Y., Huber, R., and Kohno, J. 2001. Crystal structure of the 20S proteasome:TMC-95A complex: a non-covalent proteasome inhibitor. J. Mol. Biol. 311:543-548.