Ajuga decumbens stimulates mesenchymal stem cell differentiation and regenerates cartilage in a rabbit osteoarthritis model

In a previous study by our group, Ajuga decumbens extract (ADE) was demonstrated to decrease the number of osteoclasts in subchondral bone and to have a synergistic effect with glucosamine in improving cartilaginous injuries in a rabbit model of osteoarthritis. In the present study, a concentrate of the useful fraction of ADE, termed extra ADE (EADE), which includes higher concentrations of the active component 20-hydroxyecdysone, was evaluated for its efficacy to accelerate the healing of experimental cartilage injury. Cartilage injuries were surgically induced in rabbits by creating three holes; one in the articular cartilage of the medial trochlea and two in the trochlear sulcus of the distal femur. The rabbits were divided into the following four groups (n=3 in each): Control, ADE (0.5 g/kg), low dosage EADE (0.05 g/kg; low EADE) and high dosage EADE (0.5 g/kg; high EADE). ADE and EADE were dissolved in tap water and each dosage was orally administered every day for 3 weeks. At the end of the experimental period, histological analysis indicated that the cartilage matrix was regenerated in the low and high EADE groups. On counting of cells in the histological specimens, it was determined that the mean number of osteoclasts per 100 osteoblasts in subchondral bone was lower in the high EADE group compared with the control group. Furthermore, the results indicated that treatment with EADE (1–100 µg/ml) stimulated chondrogenic differentiation of mesenchymal stem cells and induced proteoglycan production to a greater extent than the control in vitro. EADE treatment (10 and 100 µg/ml) was also observed to significantly attenuate interleukin-1β-induced prostaglandin E2 production in chondrocytes (P<0.05). In summary, the results of the present study suggest that EADE may have greater curative effects on bone injury compared with the currently used therapeutic ADE.