Dissertation/ Thesis
Calcitonin Controls Bone Formation through Modulating Expression of Wnt10b in Osteoclasts
| العنوان: | Calcitonin Controls Bone Formation through Modulating Expression of Wnt10b in Osteoclasts |
|---|---|
| Alternate Title: | 抑鈣素調控破骨細胞表達Wnt10b調節骨生成作用 |
| المؤلفون: | Yen-Nien Ting, 丁延年 |
| Thesis Advisors: | Jia-Fwu Shyu, Chia-Pi Cheng, 徐佳福, 鄭珈毘 |
| سنة النشر: | 2016 |
| المجموعة: | National Digital Library of Theses and Dissertations in Taiwan |
| الوصف: | 104 Osteoporosis (OP) therapies fall into two classes (antiresorptives and anabolic drugs). Bisphosphonates (BP) is one kind of antiresorptive. However, the antiresorptive effect of these drugs rapidly decreases bone formation and tissue turnover, which limits the gain in bone mineral density. Our recent results indicated that calcitonin (CT) inhibited BP-induced osteoclast apoptosis and combined usage of BP increased their efficacy to treat osteoporotic rats. These suggest that different kinds of antiresorptives may induce different osteoclast- derived bone formation-stimulating factors (clastokines). Wnt10b is recent identified one kind of clastokine and potential novel therapeutic target of OP. We hypothesize that uncoupling antiresorptives such as CT increase bone formation by inducing Wnt10b expression in osteoclasts. For this, we evaluate the physiological role of Wnt10b in bone remodeling and its potential as novel therapeutic target of postmenopausal OP. We isolated monocyte from Sprague Dawley (SD) rat bone marrow, then stimulated with macrophage colony stimulating factor (MCSF) and receptor activator of nuclear factor kappa-B ligand (RANKL) to differentiate into osteoclast. Using Western blot and ELISA, increases of Wnt10b protein expression and secretion were found in CT-treated osteoclast. Using Wnt inhibitor (Wnt-C59, which can inhibit the secretion of Wnt), and we also found that CT induces an increase of Wnt10b expression in intracellular osteoclasts. Furthermore, we isolated osteoblast from neonatal SD rat calvariae. Conditioned medium collected from CT-treated osteoclasts induce osteoblastic bone formation as indicated by alizarin red stain and alkaline phosphatase stain. The immunohistochemistry analysis results of in vivo show that CT-treated ovariectomized rats increases of Wnt10b expression in trabecular bone of SD rat femur. In conclusion, CT may induce increases of bone formation through modulating expression of Wnt10b in osteoclasts. This study provides a new potential therapeutic strategy for treatment of OP and complete molecular description of the physiologic role of Wnt10b in bone remodeling. |
| Original Identifier: | 104NDMC0589005 |
| نوع الوثيقة: | 學位論文 ; thesis |
| وصف الملف: | 65 |
| الاتاحة: | http://ndltd.ncl.edu.tw/handle/39464905552997189013 |
| رقم الانضمام: | edsndl.TW.104NDMC0589005 |
| قاعدة البيانات: | Networked Digital Library of Theses & Dissertations |
| الوصف غير متاح. |