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- Title
TAK-778 induces osteogenesis in ovariectomized rats via an estrogen receptor-dependent pathway.
- Authors
Ming Cai; Yongchun Yu; Shengmei Feng; Kun Tao; Shaohua Li; Lianfu Deng; Zhengdong Cai; Cai, Ming; Yu, Yongchun; Feng, Shengmei; Tao, Kun; Li, Shaohua; Deng, Lianfu; Cai, Zhengdong
- Abstract
TAK-778, a derivative of ipriflavone, has been shown to induce bone growth both in vitro and in vivo. Recently, it has been shown that TAK-778 can enhance osteoblast differentiation of human bone marrow cells via an estrogen receptor (ER)-dependent pathway. However, the mechanism by which TAK-778 exerts its effect in vivo has not been determined. Considering the evidence that TAK-778 acts via ER-mediated signaling in vitro, in the present study we tested if TAK-778 induced osteogenesis via an ER-dependent pathway using an ovariectomized (OVX) rat model. Two weeks after test animals underwent ovariectomy, TAK-778 and/or tamoxifen was administered orally over 3 months. Vehicle-treated and sham-operated rats served as controls. The bone mineral density (BMD) of the lumbar vertebrae and sagittal two-dimensional images of the L3 vertebral body were measured. In addition, bone formation rates (BFR) and serum calcium and osteocalcin levels were measured. The results indicated that TAK-778 significantly increased BMD, serum calcium and osteocalcin levels, and BFR when compared to that of the vehicle-treated group. However, tamoxifen, a well-known ER antagonist, clearly inhibited the increase in these parameters induced by TAK-778. In addition, micro-computed tomography scans showed that treatment with TAK-778 increased the structure model index, bone volume/tissue volume, and trabecular thickness parameters and decreased the trabecular separation/spacing in OVX rats. Tamoxifen suppressed these effects when administered in combination with TAK-778. Taken together, the present study showed that TAK-778 enhanced bone formation in OVX rats and that this effect was dependent on an ER-mediated pathway.
- Subjects
OSTEOGENESIS imperfecta; BONE diseases; OVARIECTOMY; LABORATORY rats; TAMOXIFEN; ESTROGEN receptors; XENOESTROGENS; PROTEIN metabolism; ANIMAL experimentation; BONE growth; COMPARATIVE studies; COMPUTED tomography; RESEARCH methodology; MEDICAL cooperation; PROTEINS; RATS; RESEARCH; SULFUR compounds; EVALUATION research; BONE density; CHEMICAL inhibitors; PHARMACODYNAMICS
- Publication
Journal of Bone & Mineral Metabolism, 2011, Vol 29, Issue 2, p168
- ISSN
0914-8779
- Publication type
journal article
- DOI
10.1007/s00774-010-0208-x