Sclerostin antibody treatment improves fracture outcomes in a Type I diabetic mouse model

Bone

Volumn 82, Issue , 2016, Pages 122-134

  Yee, Cristal S ^a,b   Xie, LiQin ^c   Hatsell, Sarah ^c   Hum, Nicholas ^a   Murugesh, Deepa ^b   Economides, Aris N ^c   Loots, Gabriela G ^a,b   Collette, Nicole M ^b  

^a LAWRENCE LIVERMORE NATIONAL LABORATORY   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c REGENERON PHARMACEUTICALS INC   (United States)

Author keywords

Fracture repair; Osteoblast differentiation; Sclerostin; Sclerostin antibody; Streptozotocin; STZ; Type I diabetes

Indexed keywords

BETA CATENIN; COLLAGEN TYPE 1; DENTIN MATRIX PROTEIN 1; OSTEOCALCIN; PROTEIN ANTIBODY; SCLEROSTIN; SCLEROSTIN ANTIBODY; TRANSCRIPTION FACTOR OSTERIX; TRANSCRIPTION FACTOR RUNX2; UNCLASSIFIED DRUG; ANTIBODY; GLYCOPROTEIN; SOST PROTEIN, MOUSE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BONE DEVELOPMENT; BONE MATRIX; BONE MINERALIZATION; CALLUS; CELL DIFFERENTIATION; CONTROLLED STUDY; DRUG EFFECT; FRACTURE; FRACTURE HEALING; IN VIVO STUDY; INSULIN DEPENDENT DIABETES MELLITUS; MALE; MOUSE; NONHUMAN; OSTEOBLAST; OSTEOPENIA; STREPTOZOTOCIN-INDUCED DIABETES MELLITUS; ANIMAL; C57BL MOUSE; COMPLICATION; DIABETES MELLITUS, TYPE 1; DRUG EFFECTS; FRACTURES, BONE; METABOLISM; PHYSIOLOGY; TREATMENT OUTCOME;

ANIMALS; ANTIBODIES; DIABETES MELLITUS, TYPE 1; FRACTURE HEALING; FRACTURES, BONE; GLYCOPROTEINS; MALE; MICE; MICE, INBRED C57BL; TREATMENT OUTCOME;

EID: 84954394462     PISSN: 87563282     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bone.2015.04.048     Document Type: Article

References (67)

1. Graves D.T., Alblowi J., Paglia D.N., O'Connor J.P., Lin S. Impact of diabetes on fracture healing. J. Exp. Clin. Med. 2011, 3:3-8.
2. Hamilton E.J., Rakic V., Davis W.A., Chubb S.A., Kamber N., Prince R.L., Davis T.M. Prevalence and predictors of osteopenia and osteoporosis in adults with Type 1 diabetes. Diabet. Med. 2009, 26:45-52. (PMID: 19125760).
3. McCabe L.R. Understanding the pathology and mechanisms of Type I diabetic bone loss. J. Cell. Biochem. 2007, 102:1343-1357. (PMID: 17975793).
4. Hofbauer L.C., Brueck C.C., Singh S.K., Bobnig H. Osteoporosis in patients with diabetes mellitus. J. Bone Miner. Res. Sep 2007, 22(9):1317-1328. (PMID: 17501667).
5. Nyman J.S., Even J.L., Jo C.H., Herbert E.G., Murry M.R., Cockreil G.E., Wahl E.C., Bunn R.C., Limpkin C.K., Fowlkes J.L., Thrailkill K.M. Increasing duration of Type 1 diabetes perturbs the strength-structure relationship and increases brittleness of bone. Bone 2011, 48:733-740. (PMID: 21185416).
6. Schwartz A.V. Diabetes mellitus: does it affect bone?. Calcif. Tissue Int. 2003, 73:515-519. (PMID: 14517715).
7. Vestergaard P., Rejnmark L., Mosekilde L. Diabetes and its complications and their relationship with risk of fractures in Type 1 and 2 diabetes. Calcif. Tissue Int. 2009, 84:45-55. (PMID: 19067021).
8. Coe L.M., Irwin R., Lippner D., McCabe L.R. The bone marrow microenvironment contributes to Type 1 diabetes induced osteoblast death. J. Cell. Physiol. 2010, 226:477-483. (PMID: 20677222).
9. Iitsuka N., Hie M., Tsukamoto I. Zinc supplementation inhibits the increase in osteoclastogenesis and decrease in osteoblastogenesis in streptozotocin-induced diabetic rats. Eur. J. Pharmacol. 2013, 714:41-47. (PMID: 23735664).
10. Motyl K., McCabe L.R. Streptozotocin, Type I diabetes severity and bone. Biol. Proced. Online 2009, 11:296-315. (PMID: 19495918).
11. Hie M., Litsuka N., Otsuka T., Tsukamoto I. Insulin-dependent diabetes mellitus decreases osteoblastogenesis associated with the inhibition of Wnt signaling through increased expression of Sost and Dkk1 and inhibition of Akt activation. Int. J. Mol. Med. 2011, 28:455-462. (PMID: 21567076).
12. de Liefde I.I., van der Klift M., de Laet C.E., van Daele P.L., Hofman A., Pols H.A. Bone mineral density and fracture risk in Type-2 diabetes mellitus: the Rotterdam Study. Osteoporos. Int. 2005, 16:1713-1720. (PMID: 15940395).
13. Issa C., Zantout M.S., Azar S.T. Osteoporosis in men with diabetes mellitus. J. Osteoporos. 2011, 651867. (PMID: 21772974).
14. Shu A., Win M.T., Stein E., Cremers S., Dworakowski E., Ives R., Rubin M.R. Bone structure and turnover in Type 2 diabetes mellitus. Osteoporos. Int. 2012, 23:635-641. (PMID: 21424265).
15. Ceriello A. The emerging challenge in diabetes: the "metabolic memory". Vascul. Pharmacol. 2012, 57:133-138. (PMID: 22609133).
16. Beam H.A., Parsons J.R., Lin S.S. The effects of blood glucose control upon fracture healing in the BB Wistar rat with diabetes mellitus. J. Orthop. Res. 2002, 20:1210-1216. (PMID: 12472231).
17. Loder R.T. The Influence of Diabetes Mellitus on the Healing of Closed Fractures. Clin. Orthop. Relat. Res. 1988, 232:210-216. (PMID: 3289812).
18. Campos Pastor M.M., Lopez-Ibarra P.J., Escobar-Jimenez F., Serrano Pardo M.D., Garcia-Cervigon A.G. Intensive insulin therapy and bone mineral density in Type 1 diabetes mellitus: a prospective study. Osteoporos. Int. 2000, 11:455-459. (PMID: 10912849).
19. Petersen C.P., Reddien P.W. Wnt signaling and the polarity of the primary body axis. Cell 2009, 139:1056-1068. (PMID: 2000581).
20. Halt K., Vainio S. Coordination of kidney organogenesis by Wnt signaling. Pediatr. Nephrol. 2014, 29:737-744. (PMID: 24445433).
21. Church V.L., Francis-West P. Wnt signalling during limb development. Int. J. Dev. Biol. 2002, 46:927-936. (PMID: 12455630).
22. Chen Y., Whetstone H.C., Lin A.C., Nadesan P., Wei Q., Poon R., Alman B.A. Beta-catenin signaling plays a disparate role in different phases of fracture repair: implications for therapy to improve bone healing. PLoS Med. 2007, 4:e249. (PMID: 17676991).
23. Day T.F., Guo X., Garrett-Beal L., Yang Y. Wnt/beta-catenin signaling in mesenchymal progenitors controls osteoblast and chondrocyte differentiation during vertebrate skeletogenesis. Dev. Cell 2005, 8:739-750. (PMID: 15866164).
24. Gennari L., Merlotti D., Valenti R., Ceccarelli E., Ruvio M., Pietrini M.G., Capodarca C., Franci M.B., Campagna M.S., Calabro A., Cataldo D., Stolakis K., Dotta F., Nuti R. Circulating sclerostin levels and bone turnover in Type 1 and Type 2 diabetes. J. Clin. Endocrinol. Metab. 2012, 97:1737-1744. (PMID: 22399511).
25. Li X., Zhang Y., Kang H., Liu W., Liu P., Zhang J., Harris S.E., Wu D. Sclerostin binds to LRP5/6 and antagonizes canonical Wnt signaling. J. Biol. Chem. 2005, 280:19883-19887. (PMID: 15778503).
26. Loots G.G., Kneissel M., Keller H., Baptist M., Chang J., Collette N.M., Ovcharenko D., Plajzer-Frick I., Rubin E.M. Genomic deletion of a long-range bone enhancer mistregulates sclerostin in Van Buchem disease. Genome Res. 2005, 15:928-935. (PMID: 15965026).
27. Collette N.M., Genetos D.C., Murugesh D., Harland R.M., Loots G.G. Genetic evidence that Sost inhibits Wnt signaling in the limb. Dev. Biol. 2010, 342:169-179. (PMID: 20359476).
28. Collette N.M., Genetos D.C., Economides A.N., Xie L., Shahnazari M., Yao W., Lane N.E., Harland R.M., Loots G.G. Targeted deletion of Sost distal enhancer increases bone formation and bone mass. Proc. Natl. Acad. Sci. U. S. A. 2012, 109:14092-14097. (PMID: 22886088).
29. Li X., Ominsky M.S., Niu Q.T., Sun N., Daugherty B., D'Agostin D., Kurahara C., Gao Y., Cao J., Gong J., Asuncion F., Barrero M., Warmington K., Dwyer D., Stolina M., Morony S., Sarosi I., Kostenuik P.J., Lacey D.L., Simonet W.S., Ke H.Z., Paszty C. Targeted deletion of the sclerostin gene in mice results in increased bone formation and bone strength. J. Bone Miner. Res. 2008, 23:860-869. (PMID: 18269310).
30. Brunkow M.E., Gardner J.C., Van Ness J., Paeper B.W., Kovacevich B.R., Proll S., Skonier J.E., Zhao L., Sabo P.J., Fu Y., Alisch R.S., Gillett L., Colbert T., Tacconi P., Galas D., Hamersma H., Beighton P., Mulligan J. Bone dysplasia sclerosteosis results from loss of the SOST gene product, a novel cystine knot-containing protein. Am. J. Hum. Genet. 2001, 68:577-589. (PMID: 11179006).
31. Balemans W., Van Den Ende J., Freire Paes-Alves A., Dikkers F.G., Willems P.J., Vanhoenacker F., de Almeida-Melo N., Alves C.F., Stratakis C.A., Hill S.C., Van Hul W. Localization of the gene for sclerosteosis to the van Buchem disease-gene region on chromosome 17q12-q21. Am. J. Hum. Genet. 1999, 64:1661-1669. (PMID: 10330353).
32. Balemans W., Patel N., Ebeling M., Van Hul E., Wuyts W., Lacza C., Dioszegi M., Dikkers F.G., Hildering P., Willems P.J., Verheij J.B., Lindpaintner K., Vickery B., Foernzler D., Van Hul W. Identification of a 52kb deletion downstream of the SOST gene in patients with van Buchem disease. J. Med. Genet. 2002, 39:91-97. (PMID: 11836356).
33. Suen P.K., He Y., Chow D.H.K., Huang L., Li C., Ke H.Z., Ominsky M.S., Qin L. Sclerostin monoclonal antibody enhanced bone fracture healing in an open osteotomy model in rats. J. Orthop. Res. 2014, 32:997-1005. (PMID: 24782158).
34. McDonald M.M., Morse A., Mkulec K., Peacock L., Yu N., Baldock P.A., Birke O., Liu M., Ke H.Z., Little D.G. Inhibition of sclerostin by systemic treatment with sclerostin antibody enhances healing of proximal tibial defects in ovariectomized rats. J. Orthop. Res. 2012, 30:1542-1548. (PMID: 22457198).
35. Hamann C., Rauner M., Höhna Y., Bernhardt R., Mettelsiefen J., Goettsch C., Günther K.P., Stolina M., Han C.Y., Asuncion F.J., Ominsky M.S., Hofbauer L.C. Sclerostin antibody treatment improves bone mass, bone strength, and bone defect regeneration in rats with Type 2 diabetes mellitus. J. Bone Miner. Res. 2013, 28:627-638. (PMID: 23109114).
36. Bonnarens F., Einhorn T.A. Production of a standard closed fracture in laboratory animal bone. J. Orthop. Res. 1984, 2:97-101. (PMID: 6491805).
37. Bouxsein M.L., Boyd S.K., Christiansen B.A., Guldberg R.E., Jepsen K.J., Müller R. Guidelines for assessment of bone microstructure in rodents using micro-computed tomography. J. Bone Miner. Res. 2010, 25:1468-1486. (PMID: 20533309).
38. Glatt V., Canalis E., Stadmeyer L., Bouxsein M.L. Age-related changes in trabecular architecture differ in female and male C57BL/6J mice. J. Bone Miner. Res. 2007, 22:1197-1207. (PMID: 17488199).
39. Hamada Y., Kitazawa S., Kitazawa R., Fujii H., Kasuga M., Fukagawa M. Histomorphometric analysis of diabetic osteopenia in streptozotocin-induced diabetic mice: a possible role of oxidative stress. Bone 2007, 40:1408-1414. (PMID: 17251074).
40. Fowlkes J.L., Nyman J.S., Bunn R.C., Jo C., Wahl E.C., Liu L., Cockrell G.E., Morris L.M., Lumpkin C.K., Thrailkill K.M. Osteo-promoting effects of insulin-like growth factor I (IGF-I) in a mouse model of type 1 diabetes. Bone 2013, 57:36-40. (PMID: 23886838).
41. López-Herradón A., Portal-Núñez S., García-Martín A., Lozano D., Pérez-Martínez F.C., Ceña V., Esbrit P. Inhibition of the canonical Wnt pathway by high glucose can be reversed by parathyroid hormone-related protein in osteoblastic cells. J. Cell. Biochem. 2013, 114:1908-1916. (PMID: 23494914).
42. Ellies D.L., Viviano B., McCarthy J., Rey J.P., Itasaki N., Saunders S., Krumlauf R. Bone density ligand, Sclerostin, directly interacts with LRP5 but not LRP5G171V to modulate Wnt activity. J. Bone Miner. Res. 2006, 21:1738-1749. (PMID: 17002572).
43. Chuang C.C., Yang R.S., Tsai K.S., Ho F.M., Liu S.H. Hyperglycemia enhances adipogenic induction of lipid accumulation: involvement of extracellular signal-regulated protein kinase 1/2, phosphoinositide 3-kinase/Akt, and peroxisome proliferator-activated receptor gamma signaling. Endocrinology 2007, 148:4267-4275. (PMID: 17540722).
44. Wang A., Midura R.J., Vasanji A., Wang A.J., Hascall V.C. Hyperglycemia diverts dividing osteoblastic precursor cells to an adipogenic pathway and induces synthesis of a hyaluronan matrix that is adhesive for monocytes. J. Biol. Chem. 2014, 289:11410-11420. (PMID: 24569987).
45. Botolin S., McCabe L.R. Bone loss and increased bone adiposity in spontaneous and pharmacologically induced diabetic mice. Endocrinology 2007, 148:198-205. (PMID: 17053023).
46. Musumeci G., Loreto C., Clementi G., Fiore C.E., Martinez G. An in vivo experimental study on osteopenia in diabetic rats. Acta Histochem. 2011, 113:619-625. (PMID: 20696468).
47. Lozano D., Fernández-de-Castro L., Portal-Núñez S., López-Herradón A., Dapía S., Gómez-Barrena E., Esbrit P. The C-terminal fragment of parathyroid hormone-related peptide promotes bone formation in diabetic mice with low-turnover osteopaenia. Br. J. Pharmacol. 2011, 162:1424-1438. (PMID: 21175568).
48. Ross R.D., Edwards L.H., Acerbo A.S., Ominsky M.S., Virdi A.S., Sena K., Miller L.M., Sumner D.R. Bone matrix quality after sclerostin antibody treatment. J. Bone Miner. Res. 2014, 29:1597-1607. (PMID: 24470143).
49. Hassler N., Roschger A., Gamsjaeger S., Kramer I., Lueger S., van Lierop A., Roschger P., Klaushofer K., Paschalis E.P., Kneissel M., Papapoulos S. Sclerostin deficiency is linked to altered bone composition. J. Bone Miner. Res. 2014, 29:2144-2151. (PMID: 24753092).
50. Ominsky M.S., Li C., Li X., Tan H.L., Lee E., Barrero M., Asuncion F.J., Dwyer D., Han C.Y., Vlasseros F., Samadfam R., Jolette J., Smith S.Y., Stolina M., Lacey D.L., Simonet W.S., Paszty C., Li G., Ke H.Z. Inhibition of sclerostin by monoclonal antibody enhances bone healing and improves bone density and strength of nonfractured bones. J. Bone Miner. Res. 2011, 26:1012-1021. (PMID: 21542004).
51. Jawad M.U., Fritton K.E., Ma T., Ren P.G., Goodman S.B., Ke H.Z., Babij P., Genovese M.C. Effects of sclerostin antibody on healing of a non-critical size femoral bone defect. J. Orthop. Res. 2013, 31:155-163. (PMID: 22887736).
52. Li C., Ominsky M.S., Tan H.L., Barrero M., Niu Q.T., Asuncion F.J., Lee E., Liu M., Simonet W.S., Paszty C., Ke H.Z. Increased callus mass and enhanced strength during fracture healing in mice lacking the sclerostin gene. Bone 2011, 49:1178-1185. (PMID: 21890008).
53. Feng G., Chang-Qing Z., Yi-Min C., Xiao-Lin L. Systemic administration of sclerostin monoclonal antibody accelerates fracture healing in the femoral osteotomy model of young rats. Int. Immunopharmacol. 2015, 24:7-13. (PMID: 25479724).
54. Lu H., Kraut D., Gerstenfeld L.C., Graves D.T. Diabetes interferes with the bone formation by affecting the expression of transcription factors that regulate osteoblast differentiation. Endocrinology 2003, 144:346-352. (PMID: 12488363).
55. Song L., Liu M., Ono N., Bringhurst F.R., Kronenberg H.M., Guo J. Loss of Wnt/β-catenin signaling causes cell fate shift of preosteoblasts from osteoblasts to adipocytes. J. Bone Miner. Res. 2012, 27:2344-2358. (PMID: 22729939).
56. Zhang Q., Riddle R.C., Clemens T.L. Bone and the regulation of global energy balance. J. Intern. Med. Jan 16 2015, (Epub ahead of print, PMID: 25597336). 10.1111/joim.12348.
57. Liang J., Slingerland J.M. Multiple roles of the PI3K/PKB(Akt) pathway in cell cycle progression. Cell Cycle 2003, 2:339-345. (PMID: 12851486).
58. Kim J.Y., Lee S.K., Jo K.J., Song D.Y., Lim D.M., Park K.Y., Bonewald L.F., Kim B.J. Exendin-4 increases bone mineral density in Type 2 diabetic OLETF rats potentially through the down-regulation of SOST/sclerostin in osteocytes. Life Sci. 2013, 92:533-540. (PMID: 23357248).
59. Ma P., Gu B., Xiong W., Tan B., Geng W., Li J., Liu H. Glimepiride promotes osteogenic differentiation in rat osteoblasts via the PI3K/Akt/eNOS pathway in a high glucose microenvironment. PLoS One 2014, 9:e112243. (PMID: 25391146).
60. Erejuwa O.O. Management of diabetes mellitus: could simultaneous targeting of hyperglycemia and oxidative stress be a better panacea?. Int. J. Mol. Sci. 2012, 13:2965-2972. (PMID: 22489136).
61. Manolagas S.C., Almeida M. Gone with the Wnts: beta-catenin, T-cell factor, forkhead box O, and oxidative stress in age-dependent diseases of bone, lipid, and glucose metabolism. Mol. Endocrinol. 2007, 21:2605-2614. (PMID: 17622581).
62. Gaudio A., Privitera F., Battaglia K., Torrisi V., Sidoti M.H., Pulvirenti I., Canzonieri E., Tringali G., Fiore C.E. Sclerostin levels associated with inhibition of the Wnt/β-catenin signaling and reduced bone turnover in Type 2 diabetes mellitus. J. Clin. Endocrinol. Metab. 2012, 97:3744-3750. (PMID: 22855334).
63. Abiola M., Favier M., Christodoulou-Vafeiadou E., Pichard A.L., Martelly I., Guillet-Deniau I. Activation of Wnt/beta-catenin signaling increases insulin sensitivity through a reciprocal regulation of Wnt10b and SREBP-1c in skeletal muscle cells. PLoS One 2009, 4:e8509. (PMID: 20041157).
64. Stolina M., Dwyer D., Niu Q.T., Villasenor K.S., Kurimoto P., Grisanti M., Han C.Y., Liu M., Li X., Ominsky M.S., Ke H.Z., Kostenuik P.J. Temporal changes in systemic and local expression of bone turnover markers during six months of sclerostin antibody administration to ovariectomized rats. Bone 2014, 67:305-313. (PMID: 25093263).
65. Ominsky M.S., Vlasseros F., Jolette J., Smith S.Y., Stouch B., Doellgast G., Gong J., Gao Y., Cao J., Graham K., Tipton B., Cai J., Deshpande R., Zhou L., Hale M.D., Lightwood D.J., Henry A.J., Popplewell A.G., Moore A.R., Robinson M.K., Lacey D.L., Simonet W.S., Paszty C. Two doses of sclerostin antibody in cynomolgus monkeys increases bone formation, bone mineral density, and bone strength. J. Bone Miner. Res. 2010, 25:948-959. (PMID: 20200929).
66. Padhi D., Jang G., Stouch B., Fang L., Posvar E. Single-dose, placebo-controlled, randomized study of AMG 785, a sclerostin monoclonal antibody. J. Bone Miner. Res. 2011, 26:19-26. (PMID: 20593411).
67. van Dinther M., Zhang J., Weidauer S.E., Boschert V., Muth E.M., Knappik A., de Gorter D.J., van Kasteren P.B., Frisch C., Mueller T.D., ten Dijke P. Anti-sclerostin antibody inhibits internalization of sclerostin and sclerostin-mediated antagonism of Wnt/LRP6 signaling. PLoS One 2013, 8:e62295. (PMID: 23638027).