ecdysterone and Osteoarthritis--Knee

β-Ecdysone has been reported to perform a protective effect to prevent interleukin 1β (IL-1β)-induced apoptosis and inflammatory response in chondrocytes. In our study, the chondroprotective effects of β-Ecdysone were explored in a mouse model of collagenase-induced osteoarthritis (OA).. Injection of collagenase in the left knee was implemented to establish a mouse model of OA. The histomorphological analysis was detected using safranine O staining. Serum pro-inflammatory cytokines were measured by ELISA assays. Protein expression in the femur and chondrocytes was analyzed using western blot. Chondrocyte apoptosis was evaluated by terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) staining.. Treatment of OA mice with β-Ecdysone supplementation significantly inhibited the production of pro-inflammatory cytokines. Histologic examination exhibited that the degradation of proteoglycans and the loss of trabecular bone were observed in collagenase-injected mice. However, OA-like changes were attenuated by β-Ecdysone administration in collagenase-injected mice. Both in vivo and in vitro models, nuclear forkhead box O1 (FOXO1) protein expression was significantly reduced in the femur of collagenase-treated mice and IL-1β-stimulated chondrocytes. However, β-Ecdysone treatment was able to rescue FOXO1 protein expression in the nucleus to inhibit the transcription and translation of a disintegrin-like and metallopeptidase (reprolysin type) with thrombospondin type 1 motif, 4 (ADAMTS-4) and ADAMTS-5.. The findings suggested that β-Ecdysone functioned as a FOXO1 activator to protect collagenase-induced cartilage damage. FOXO1 might be a potential molecular target of β-Ecdysone for the effective prevention and treatment of OA.

Topics: ADAMTS4 Protein; ADAMTS5 Protein; Animals; Arthritis, Experimental; Cartilage, Articular; Ecdysterone; Forkhead Box Protein O1; Mice; Osteoarthritis, Knee; Signal Transduction

Ecdysteroids are steroids found in invertebrates and plants. In mammals they have protein anabolic effects. We have recently published antiosteoporotic effects of Tinospora cordifolia (TC) extract and the search for the possible active ingredients yielded the presence of beta-Ecdysone (Ecd). Therefore, we investigated the effects of pure Ecd in ovariectomized rats on morphological changes in joint, epiphyseal cartilage and trabecular tissue. Following ovariectomy rats were fed for 1 month with Ecd containing food at a dose of 52.8 mg/day/animal. Positive and negative control animals received 17-beta Estradiol (E(2), 132 microg/day/animal) and soy free (sf) food respectively. At sacrifice, specimens consisting of upper tibiae-lower femurs and knee joint were harvested and processed for histomorphometry. The parameters measured included thickness of the joint cartilage, thickness of the whole epiphyseal growth plate and its three zones. Furthermore, the percentage of trabecular bone in the metaphysis region of tibiae was quantified. Ecd and E(2) induced a significant increase in the thickness of joint cartilage. The whole epiphyseal growth plate and its proliferative and hypertrophic zones were also increased by Ecd whereas E(2) reduced their size. The percentage of trabecular area in the metaphysis of tibia was significantly increased in Ecd and E(2) treated animals. Results provide a plausible explanation for the antiosteoporotic effects of TC. Hence, TC as well as other Ecd producing plants or pure Ecd may be of value in the prevention and treatment of osteoporosis and osteoarthritis which is of increasing importance due to aging and obesity among individuals.

Topics: Animals; Bone and Bones; Bone Density; Bone Density Conservation Agents; Diet; Drug Therapy, Combination; Ecdysterone; Estradiol; Female; Femur; Growth Plate; Knee Joint; Osteoarthritis, Knee; Osteoporosis; Ovariectomy; Phytotherapy; Plant Extracts; Rats; Rats, Wistar; Soy Foods; Tibia; Tinospora