Summary
Recent studies have shown that Er-Zhi-Wan (EZW), a traditional Chinese medicine consisting of Herba Ecliptae (HE) and Fructus Ligustri Lucidi (FLL), had a definite antiosteoporotic effect on osteoporotic femur, but its effect on osteoporosis of alveolar bone remains unknown. In the present study, we investigated the effects of Er-Zhi-Wan (EZW) on the microarchitecture and the regulation of Wnt/β-catenin signaling pathway in the alveolar bone of ovariectomized rats. Thirty Sprague-Dawley rats were randomly divided into three groups: sham operation group (sham, n=10), ovariectomy (OVX) group (n=10), and OVX with EZW treatment group (EZW group, n=10). From one week after ovariectomy, EZW (100 mg/mL) or vehicle (distilled water) was fed (1 mL/100 g) once per day for 12 weeks until the sacrifice of the rats. The body weights were measured weekly. After sacrifice, the sera and mandible were collected and routinely prepared for the measurement of alveolar trabecular microarchitecture, serum levels of E2, bone-specific alkaline phosphatase (BALP) and tartrate-resistant acid phosphatase 5b (TRAP5b), as well as mandibular mRNA expression of Wnt/β-catenin signaling pathway molecules wnt3a, low-density lipoprotein receptor-related protein 5 (LRP5), β-catenin and dickkopf homolog 1 (DKK1). The results showed that EZW treatment significantly prevented the body weight gain, degradation of alveolar trabecular microarchitecture and alveolar bone loss in the OVX rats. Furthermore, we observed that EZW could increase the serum levels of E2 and BALP, and decrease levels of serum TRAP5b in EZW group compared with vehicle group. In addition, RT-PCR results revealed that EZW upregulated the expression levels of wnt3a, LRP5 and β-catenin, and reduced the expression of DKK1 in OVX rats. Taken together, our results suggested that EZW may have potential anti-osteoporotic effects on osteoporotic alveolar bone by stimulating Wnt/LRP5/β-catenin signaling pathway.
References
Birkenfeld L, Yemini M, Kase NG, et al. Menopause- related oral alveolar bone resorption: a review of relatively unexplored consequences of estrogen deficiency. Menopause, 1999,6(2):129–133
Hildebolt CF. Osteoporosis and oral bone loss. Dentomaxillofac Radiol, 1997,26(1):3–15
Payne JB, Reinhardt RA, Nummikoski PV, et al. Longitudinal alveolar bone loss in postmenopausal osteoporotic/osteopenic women. Osteoporos Int, 1999,10(1): 34–40
Tanaka M, Ejiri S, Toyooka E, et al. Effects of ovariectomy on trabecular structures of rat alveolar bone. J Periodontal Res, 2002,37(2):161–165
Tanaka M, Toyooka E, Kohno S, et al. Long-term changes in trabecular structure of aged rat alveolar bone after ovariectomy. Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 2003,95(4):495–502
Stevenson JC. Justification for the use of HRT in the long-term prevention of osteoporosis. Maturitas, 2005,51(2):113–126
Prelevic GM, Kocjan T, Markou A. Hormone replacement therapy in postmenopausal women. Minerva Endocrinol, 2005,30(1):27–36
Cheng M, Wang Q, Fan Y, et al. A traditional Chinese herbal preparation, Er-Zhi-Wan, prevent ovariectomy-induced osteoporosis in rats. J Ethnopharmacol, 2011,138(2):279–285
Zhang H, Xing WW, Li YS, et al. Effects of a traditional Chinese herbal preparation on osteoblasts and osteoclasts. Maturitas, 2008,61(4):334–339
Xu H, Su ZR, Huang W, et al. Er Zhi Wan, an ancient herbal decoction for woman menopausal syndrome, activates the estrogenic response in cultured MCF-7 cells: an evaluation of compatibility in defining the optimized preparation method. J Ethnopharmacol, 2012,143(1): 109–115
Hoeppner LH, Secreto FJ, Westendorf JJ. Wnt signaling as a therapeutic target for bone diseases. Expert Opin Ther Targets, 2009,13(4):485–496
Kulkarni NH, Onyia JE, Zeng Q, et al. Orally bioavailable GSK-3alpha/beta dual inhibitor increases markers of cellular differentiation in vitro and bone mass in vivo. J Bone Miner Res, 2006,21(6):910–920
Kalu DN. The ovariectomized rat model of postmenopausal bone loss. Bone Miner, 1991,15(3):175–191
Gilles JA, Carnes DL, Dallas MR, et al. Oral bone loss is increased in ovariectomized rats. J Endod, 1997,23(7): 419–422
Sugimoto M, Futaki N, Harada M, et al. Effects of combined treatment with eldecalcitol and alendronate on bone mass, mechanical properties, and bone histomorphometry in ovariectomized rats: a comparison with alfacalcidol and alendronate. Bone, 2013,52(1):181–188
Cavani F, Ferretti M, Carnevale G, et al. Effects of different doses of ferutinin on bone formation/resorption in ovariectomized rats. J Bone Miner Metab, 2012,30(6): 619–629
Peng S, Liu XS, Wang T, et al. In vivo anabolic effect of strontium on trabecular bone was associated with increased osteoblastogenesis of bone marrow stromal cells. J Orthop Res, 2010,28(9):1208–1214
Eren E, Yilmaz N. Biochemical markers of bone turnover and bone mineral density in patients with beta-thalassaemia major. Int J Clin Pract, 2005,59(1):46–51
Dervis E. Oral implications of osteoporosis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 2005,100(3): 349–356
Seeman E, Delmas PD. Bone quality—the material and structural basis of bone strength and fragility. N Engl J Med, 2006,354(21):2250–2261
McDonnell P, McHugh PE, O’Mahoney D. Vertebral osteoporosis and trabecular bone quality. Ann Biomed Eng, 2007,35(2):170–189
Li Y, Li X, Song G, et al. Effects of strontium ranelate on osseointegration of titanium implant in osteoporotic rats. Clin Oral Implants Res, 2012,23(9):1038–1044
Huja SS, Fernandez SA, Hill KJ, et al. Indentation modulus of the alveolar process in dogs. J Dent Res, 2007,86(3):237–241
Ames MS, Hong S, Lee HR, et al. Estrogen deficiency increases variability of tissue mineral density of alveolar bone surrounding teeth. Arch Oral Biol, 2010,55(8): 599–605
Yang J, Pham SM, Crabbe DL. Effects of oestrogen deficiency on rat mandibular and tibial microarchitecture. Dentomaxillofac Radiol, 2003,32(4):247–251
Marie PJ, Kassem M. Osteoblasts in osteoporosis: past, emerging, and future anabolic targets. Eur J Endocrinol, 2011,165(1):1–10
Krishnan V, Bryant HU, Macdougald OA. Regulation of bone mass by Wnt signaling. J Clin Invest, 2006,116(5): 1202–1209
Bodine PV, Komm BS. Wnt signaling and osteoblastogenesis. Rev Endocr Metab Disord, 2006,7(1–2):33–39
Author information
Authors and Affiliations
Corresponding author
Additional information
The authors contributed equally to this work.
This project was supported by grants from the National Natural Science Foundation of China (No. 81170992) and the Fundamental Research Funds for the Central Universities of Wuhan University (No. 201130402020004).
Rights and permissions
About this article
Cite this article
Sun, W., Wang, Yq., Yan, Q. et al. Effects of Er-Zhi-Wan on microarchitecture and regulation of Wnt/β-catenin signaling pathway in alveolar bone of ovariectomized rats. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 34, 114–119 (2014). https://doi.org/10.1007/s11596-014-1241-0
Received:
Revised:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11596-014-1241-0