Abstract
We investigated the effect of in vitro cultured Wnt3a-producing fibroblasts on positive bone balance and regeneration of the osteopenic skeleton. Thirty-six female Wistar rats (250–300 g, aged 12 weeks) were randomized into three groups: a control group (sham-operated), ovariectomy (OVX) group, and OVX with Wnt-cell injection (OVX with Wnt) group. Wnt3a-producing fibroblasts were injected into the lateral tail vein at 2 and 4 weeks after OVX. Both tibias were removed at 5, 6, 7, and 8 weeks after OVX, and pathological and micro-CT evaluations were performed. We also evaluated β-catenin expression by immunohistochemical staining. For bone metabolism detection, we evaluated the expression of bone alkaline phosphatase (BALP), osteocalcin, and C-telopeptide of collagen type I. Bone mineral density, trabecular bone volume, trabecular number, trabecular thickness were higher, while trabecular seperation was lower, in the OVX with Wnt group than in the OVX group. BALP and osteocalcin levels were significantly higher in the OVX with Wnt group compared to the control and OVX groups. β-catenin expression was significantly lower in the OVX group than in the other two groups. Based on these results, we hypothesized that Wnt3a-producing fibroblasts may be effective for the induction of bone formation.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Khosla S, Riggs BL. Pathophysiology of age-related bone loss and osteoporosis. Endocrinol Metab Clin North Am 2005;34:1015–1030, xi.
Voskaridou E, Terpos E. New insights into the pathophysiology and management of osteoporosis in patients with beta thalassaemia. Br J Haematol 2004;127:127–139.
Christenson RH. Biochemical markers of bone metabolism: an overview. Clin Biochem 1997;30:573–593.
Kanis JA. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis: synopsis of a WHO report. WHO Study Group. Osteoporos Int 1994;4:368–381.
Jeong JH, Park JR, Jin ES, Min JK, Jeon SR, Kim DK, et al. Adipose tissuederived stem cells in the ovariectomy-induced postmenopausal osteoporosis rat model. Tissue Eng Regen Med 2015;12:28–36.
Huelsken J, Behrens J. The Wnt signalling pathway. J Cell Sci 2002;115(Pt 21):3977–3978.
Logan CY, Nusse R. The Wnt signaling pathway in development and disease. Annu Rev Cell Dev Biol 2004;20:781–810.
Toledo EM, Colombres M, Inestrosa NC. Wnt signaling in neuroprotection and stem cell differentiation. Prog Neurobiol 2008;86:281–296.
Im GI. Intracellular signal transduction pathways and transcription factors for osteogenesis. J Korean Rheum Assoc 2008;15:1–10.
Im J, Kim H, Kim S, Jho EH. Wnt/beta-catenin signaling regulates expression of PRDC, an antagonist of the BMP-4 signaling pathway. Biochem Biophys Res Commun 2007;354:296–301.
Yun S, Rim Y, Jho EH. Induced expression of the transcription of tropomodulin 1 by Wnt5a and characterization of the tropomodulin 1 promoter. Biochem Biophys Res Commun 2007;363:727–732.
Cho SW, Sun HJ, Yang JY, Jung JY, Choi HJ, An JH, et al. Human adipose tissue-derived stromal cell therapy prevents bone loss in ovariectomized nude mouse. Tissue Eng Part A 2012;18:1067–1078.
Moon RT, Kohn AD, De Ferrari GV, Kaykas A. WNT and beta-catenin signalling: diseases and therapies. Nat Rev Genet 2004;5:691–701.
Reya T, Clevers H. Wnt signalling in stem cells and cancer. Nature 2005; 434:843–850.
Nusse R, Varmus HE. Many tumors induced by the mouse mammary tumor virus contain a provirus integrated in the same region of the host genome. Cell 1982;31:99–109.
Rijsewijk F, Schuermann M, Wagenaar E, Parren P, Weigel D, Nusse R. The Drosophila homolog of the mouse mammary oncogene int-1 is identical to the segment polarity gene wingless. Cell 1987;50:649–657.
Nusse R, Brown A, Papkoff J, Scambler P, Shackleford G, McMahon A, et al. A new nomenclature for int-1 and related genes: the Wnt gene family. Cell 1991;64:231.
Gong Y, Slee RB, Fukai N, Rawadi G, Roman-Roman S, Reginato AM, et al. LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development. Cell 2001;107:513–523.
Gong Y, Vikkula M, Boon L, Liu J, Beighton P, Ramesar R, et al. Osteoporosis-pseudoglioma syndrome, a disorder affecting skeletal strength and vision, is assigned to chromosome region 11q12-13. Am J Hum Genet 1996; 59:146–151.
Pinson KI, Brennan J, Monkley S, Avery BJ, Skarnes WC. An LDL-receptor-related protein mediates Wnt signalling in mice. Nature 2000;407: 535–538.
Tamai K, Semenov M, Kato Y, Spokony R, Liu C, Katsuyama Y, et al. LDLreceptor-related proteins in Wnt signal transduction. Nature 2000;407: 530–535.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Jeong, J.H., Jin, ES., Min, J. et al. Wnt3a-producing fibroblasts in ovariectomy-induced osteoporosis in a rat model. Tissue Eng Regen Med 12, 306–313 (2015). https://doi.org/10.1007/s13770-014-0074-z
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13770-014-0074-z