- 著者
- Jiajun Lyu Takuya Kubo Sayuki Iwahashi Kazuya Fukasawa Tetsuhiro Horie Katashi Nagamatsu Kumiko Ikeno Genjiro Nakamura Masaki Kamakura Eiichi Hinoi
- 出版者
- The Pharmaceutical Society of Japan
- 雑誌
- Biological and Pharmaceutical Bulletin (ISSN:09186158)
- 巻号頁・発行日
- vol.46, no.2, pp.348-353, 2023-02-01 (Released:2023-02-01)
- 参考文献数
- 32
Royal jelly (RJ), an essential food for the queen honeybee, has a variety of biological activities. Although RJ exerts preventive effects on various lifestyle-related diseases, such as osteoporosis and obesity, no study evaluated the effect of RJ on the development of osteoarthritis (OA), the most common degenerative joint disease. Here, we showed that daily oral administration of raw RJ significantly prevented OA development in vivo following surgically-induced knee joint instability in mice. Furthermore, in vitro experiments using chondrocytes, revealed that raw RJ significantly reduced the expression of inflammatory cytokines and enzymes critical for the degradation of the extracellular matrix (ECM). Similar results were observed after treatment with 10-hydroxy-2-decenoic acid, the most abundant and unique fatty acid in raw RJ. Our results suggest that oral supplementation with RJ would benefit the maintenance of joint health and prophylaxis against OA, possibly by suppressing the activity of inflammatory cytokines and ECM-degrading enzymes.
- 著者
- Megumi Yamamoto Yuma Ito Masaki Fukui Kazuya Otake Yoshimichi Shoji Tatsuya Kitao Hiroaki Shirahase Eiichi Hinoi
- 出版者
- The Pharmaceutical Society of Japan
- 雑誌
- Biological and Pharmaceutical Bulletin (ISSN:09186158)
- 巻号頁・発行日
- vol.46, no.10, pp.1435-1443, 2023-10-01 (Released:2023-10-01)
- 参考文献数
- 35
- 被引用文献数
- 1
Osteoporosis is treated with oral and parenteral bone resorption inhibitors such as bisphosphonates, and parenteral osteogenic drugs including parathyroid hormone (PTH) analogues and anti-sclerostin antibodies. In the present study, we synthesized KY-054, a 4,6-substituted coumarin derivative, and found that it potently promoted osteoblast differentiation with an increase in alkaline phosphatase (ALP) activity at 0.01–1 µM in mouse-derived mesenchymal stem cells (ST2 cells) and rat bone marrow-derived mesenchymal stem cells (BMSCs). In the ovariectomized (OVX) rats, KY-054 (10 mg/kg/d, 8 weeks) increased plasma bone-type ALP activity, suggesting in vivo promoting effects on osteoblast differentiation and/or activation. In dual-energy X-ray absorption (DEXA) scanning, KY-054 significantly increased the distal and diaphyseal femurs areal bone mineral density (aBMD) that was decreased by ovariectomy, indicating its beneficial effects on bone mineral contents (BMC) and/or bone volume (BV). In micro-computed tomography (micro-CT) scanning, KY-054 had no effect on metaphysis trabecular bone loss and microarchitecture parameters weakened by ovariectomy, but instead increased metaphysis and diaphysis cortical bone volume (Ct.BV) and cortical BMC (Ct.BMC) without reducing medullary volume (Med.V), resulting in increased bone strength parameters. It is concluded that KY-054 preferentially promotes metaphysis and diaphysis cortical bone osteogenesis with little effect on metaphysis trabecular bone resorption, and is a potential orally active osteogenic anti-osteoporosis drug candidate.
- 著者
- Eiichi Hinoi Yukio Yoneda
- 出版者
- The Japanese Pharmacological Society
- 雑誌
- Journal of Pharmacological Sciences (ISSN:13478613)
- 巻号頁・発行日
- pp.1106090573, (Released:2011-06-10)
- 参考文献数
- 67
- 被引用文献数
- 12 21
The prevailing view is that L-glutamate (Glu) functions as an excitatory amino acid neurotransmitter through a number of molecular machineries required for the neurocrine signaling at synapses in the brain. These include Glu receptors for signal input, Glu transporters for signal termination, and vesicular Glu transporters for signal output through exocytotic release. Although relatively little attention has been paid to the functional expression of these molecules required for glutamatergic signaling in peripheral tissues, recent molecular biological analyses including ours give rise to a novel function for Glu as an extracellular signal mediator in the autocrine and/or paracrine system in several peripheral and non-neuronal tissues, including bone and cartilage. In particular, a drastic increase is demonstrated in the endogenous levels of both Glu and aspartate in the synovial fluid with intimate relevance to increased edema and sensitization to thermal hyperalgesia in experimental arthritis models. However, to date, there is only limited information about the physiological and pathological significance of glutamatergic signaling machineries expressed by articular synovial tissues. In this review, we have outlined the role of Glu in synovial fibroblasts in addition to the possible involvement of glutamatergic signaling machineries in the pathogenesis of joint diseases such as rheumatoid arthritis.