Wnt3a Involved in the Mechanical Loading on Improvement of Bone Remodeling and Angiogenesis in a Postmenopausal Osteoporosis Mouse Model

Overview

Journal FASEB J

Specialties Biology
Physiology

Date 2019 Apr 25

PMID 31017804

Citations 27

Authors

Xinle Li

Daquan Liu

Jie Li

Shuang Yang

Jinfeng Xu

Hiroki Yokota

Ping Zhang

Affiliations

Soon will be listed here.

Abstract

Osteoporosis is a major health problem, making bones fragile and susceptible to fracture. Previous works showed that mechanical loading stimulated bone formation and accelerated fracture healing. Focusing on the role of Wnt3a (wingless/integrated 3a), this study was aimed to assess effects of mechanical loading to the spine, using ovariectomized (OVX) mice as a model of osteoporosis. Two-week daily application of this novel loading (4 N, 10 Hz, 5 min/d) altered bone remodeling with an increase in Wnt3a. Spinal loading promoted osteoblast differentiation, endothelial progenitor cell migration, and tube formation and inhibited osteoclast formation, migration, and adhesion. A transient silencing of Wnt3a altered the observed loading effects. Spinal loading significantly increased bone mineral density, bone mineral content, and bone area per tissue area. The loaded OVX group showed a significant increase in the number of osteoblasts and reduction in osteoclast surface/bone surface. Though expression of osteoblastic genes was increased, the levels of osteoclastic genes were decreased by loading. Spinal loading elevated a microvascular volume as well as VEGF expression. Collectively, this study supports the notion that Wnt3a-mediated signaling involves in the effect of spinal loading on stimulating bone formation, inhibiting bone resorption, and promoting angiogenesis in OVX mice. It also suggests that Wnt3a might be a potential therapeutic target for osteoporosis treatment.-Li, X., Liu, D., Li, J., Yang, S., Xu, J., Yokota, H., Zhang, P. Wnt3a involved in the mechanical loading on improvement of bone remodeling and angiogenesis in a postmenopausal osteoporosis mouse model.

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References

Makras P, Delaroudis S, Anastasilakis A . Novel therapies for osteoporosis. Metabolism. 2015; 64(10):1199-214. DOI: 10.1016/j.metabol.2015.07.011. View

Zhou Y, Guan X, Liu T, Wang X, Yu M, Yang G . Whole body vibration improves osseointegration by up-regulating osteoblastic activity but down-regulating osteoblast-mediated osteoclastogenesis via ERK1/2 pathway. Bone. 2014; 71:17-24. DOI: 10.1016/j.bone.2014.09.026. View

Zhang P, Hamamura K, Yokota H, Malacinski G . Potential applications of pulsating joint loading in sports medicine. Exerc Sport Sci Rev. 2008; 37(1):52-6. PMC: 2740904. DOI: 10.1097/JES.0b013e31819121c6. View

Mun S, Won H, Hernandez P, Aguila H, Lee S . Deletion of CD74, a putative MIF receptor, in mice enhances osteoclastogenesis and decreases bone mass. J Bone Miner Res. 2012; 28(4):948-59. PMC: 3563845. DOI: 10.1002/jbmr.1787. View

Zhang P, Yokota H . Elbow loading promotes longitudinal bone growth of the ulna and the humerus. J Bone Miner Metab. 2011; 30(1):31-9. DOI: 10.1007/s00774-011-0292-6. View

Peng J, Lai Z, Fang Z, Xing S, Hui K, Hao C . Dimethyloxalylglycine prevents bone loss in ovariectomized C57BL/6J mice through enhanced angiogenesis and osteogenesis. PLoS One. 2014; 9(11):e112744. PMC: 4231053. DOI: 10.1371/journal.pone.0112744. View

Chim S, Tickner J, Chow S, Kuek V, Guo B, Zhang G . Angiogenic factors in bone local environment. Cytokine Growth Factor Rev. 2013; 24(3):297-310. DOI: 10.1016/j.cytogfr.2013.03.008. View

Deng L, Wang Y, Peng Y, Wu Y, Ding Y, Jiang Y . Osteoblast-derived microvesicles: A novel mechanism for communication between osteoblasts and osteoclasts. Bone. 2015; 79:37-42. DOI: 10.1016/j.bone.2015.05.022. View

Li X, Liu D, Li J, Yang S, Xu J, Yokota H . Wnt3a involved in the mechanical loading on improvement of bone remodeling and angiogenesis in a postmenopausal osteoporosis mouse model. FASEB J. 2019; 33(8):8913-8924. PMC: 9272758. DOI: 10.1096/fj.201802711R. View

10.

Zhu K, Jiao H, Li S, Cao H, Galson D, Zhao Z . ATF4 promotes bone angiogenesis by increasing VEGF expression and release in the bone environment. J Bone Miner Res. 2013; 28(9):1870-1884. PMC: 4394202. DOI: 10.1002/jbmr.1958. View

11.

He Y, Childress P, Hood Jr M, Alvarez M, Kacena M, Hanlon M . Nmp4/CIZ suppresses the parathyroid hormone anabolic window by restricting mesenchymal stem cell and osteoprogenitor frequency. Stem Cells Dev. 2012; 22(3):492-500. PMC: 3549622. DOI: 10.1089/scd.2012.0308. View

12.

Li X, Yang J, Liu D, Li J, Niu K, Feng S . Knee loading inhibits osteoclast lineage in a mouse model of osteoarthritis. Sci Rep. 2016; 6:24668. PMC: 4834538. DOI: 10.1038/srep24668. View

13.

Zhao W, Xu S, Liang J, Peng L, Liu H, Wang Z . Endothelial progenitor cells from human fetal aorta cure diabetic foot in a rat model. Metabolism. 2016; 65(12):1755-1767. DOI: 10.1016/j.metabol.2016.09.007. View

14.

Reid I . Short-term and long-term effects of osteoporosis therapies. Nat Rev Endocrinol. 2015; 11(7):418-28. DOI: 10.1038/nrendo.2015.71. View

15.

Hatori K, Camargos G, Chatterjee M, Faot F, Sasaki K, Duyck J . Single and combined effect of high-frequency loading and bisphosphonate treatment on the bone micro-architecture of ovariectomized rats. Osteoporos Int. 2014; 26(1):303-13. DOI: 10.1007/s00198-014-2857-4. View

16.

Fan L, Li J, Yu Z, Dang X, Wang K . Hypoxia-inducible factor prolyl hydroxylase inhibitor prevents steroid-associated osteonecrosis of the femoral head in rabbits by promoting angiogenesis and inhibiting apoptosis. PLoS One. 2014; 9(9):e107774. PMC: 4171501. DOI: 10.1371/journal.pone.0107774. View

17.

Cheng Z, Garikipati V, Nickoloff E, Wang C, Polhemus D, Zhou J . Restoration of Hydrogen Sulfide Production in Diabetic Mice Improves Reparative Function of Bone Marrow Cells. Circulation. 2016; 134(19):1467-1483. PMC: 5101140. DOI: 10.1161/CIRCULATIONAHA.116.022967. View

18.

Lara-Castillo N, Kim-Weroha N, Kamel M, Javaheri B, Ellies D, Krumlauf R . In vivo mechanical loading rapidly activates β-catenin signaling in osteocytes through a prostaglandin mediated mechanism. Bone. 2015; 76:58-66. PMC: 4447591. DOI: 10.1016/j.bone.2015.03.019. View

19.

Xie H, Cui Z, Wang L, Xia Z, Hu Y, Xian L . PDGF-BB secreted by preosteoclasts induces angiogenesis during coupling with osteogenesis. Nat Med. 2014; 20(11):1270-8. PMC: 4224644. DOI: 10.1038/nm.3668. View

20.

Xu B, Lovre D, Mauvais-Jarvis F . Effect of selective estrogen receptor modulators on metabolic homeostasis. Biochimie. 2015; 124:92-97. DOI: 10.1016/j.biochi.2015.06.018. View