Protective effects of the Tougu Xiaotong capsule on morphology and osteoprotegerin/nuclear factor-κB ligand expression in rabbits with knee osteoarthritis

Abstract

Abstract. The imbalance of subchondral bone remodeling is a common pathological feature in the progression of osteoarthritis. In the current study, using a rabbit model of knee osteoarthritis, the effects of the Tougu Xiaotong capsule (TGXTC) on the cartilage and subchondral bone were investigated. In addition, osteoprotegerin (OPG), an inducer of bone formation, and receptor activator of nuclear factor-κB ligand (RANKL), a regulator of bone resorption in the subchondral bone, were assessed, in order to further explore the protective role of TGXTC in subchondral bone remodeling. The rabbit model of knee osteoarthritis, which was induced by a modified version of Hulth's method, was treated with TGXTC or glucosamine hydrochloride for 4 or 8 weeks. Subsequently, the tibia and femur were harvested for observation of cartilage histology, and the subchondral bone was observed by scanning electron microscopy. The expression levels of OPG and RANKL at the gene and protein levels were determined by reverse transcription-quantitative polymerase chain reaction and western blotting. TGXTC and glucosamine hydrochloride were identified to mitigate cartilage injury, reduce trabecular number and thickness and accelerate trabecular separation. It was additionally observed that the level of OPG mRNA and protein expression was reduced, and the RANKL mRNA and protein expression level was increased, in addition to the observation of a lower OPG/RANKL ratio in the TGXTC and hydrochloride groups. Taken together, these results suggest that TGXTC may mitigate cartilage injury and subchondral sclerosis, thus delaying the pathological development of osteoarthritis. This is suggested to be mediated partly through the reduction of OPG expression and increase of RANKL expression, which reduces the OPG/RANKL ratio, suppressing excessive bone formation.

Tougu Xiaotong capsule exerts a therapeutic effect on knee osteoarthritis by regulating subchondral bone remodeling

“…To this end, the literature suggests that in addition to cartilage, other articular tissues, including the subchondral bone, should be targeted. Previous findings have shown that TGXTC has therapeutic effects on knee OA (25) through multiple targets (22,23,(25)(26)(27). In this study, we investigated the effect of TGXTC on subchondral bone and its relevant mechanisms of inflammatory factors.…”

“…Tougu Xiaotong capsule (TGXTC) is an effective prescription in OA treatment which consists of Ligusticum chuanxiong, Morinda officinalis, Sarcandra glabra and Paeonia lactiflora (22,23). There are many effective molecules in TGXTC, which is multi-drug, multi-path and multi-target of molecular mechanism for the treatment of OA, and the non-linear regulation pattern exists in TGXTC ligand-target interaction network (24).…”

The Mechanism of Mitochondrial Fatty Acid Oxidation’s Involvement in Osteoporosis in Aggravating Cartilage Degeneration of Rabbit Knee Osteoarthritis

“…After BMD and BMC of the rabbit femoral head were determined, it was found that the bone mass in the OP+OA group was signi cantly reduced, and the cartilage destruction was severe, In this experiment, an experimental animal model was established by castration method combined with Hulth'S method. Rabbits were driven to walk for 30 minutes one week after modeling, which was equivalent to the middle and late stages of OA at 4 weeks [11]. Compared with the normal group, the Pelletier-JP and Minkin's scores of the joints in the OP+OA group and the OA group were signi cantly higher, indicating that the severity of the lesion is proportional to the score, and also indicating the success of this experiment.…”

Reflections about osteoarthritis and Curcuma longa

“…When there is an increase in RANKL/OPG ratio there is predominance of bone destruction, and when there is a decrease of this index, there is protection of subchondral bones. [11404142] In OA, various interleukins and cytokines such as IL-1β, IL-6, IL-11, IL-17, and TNF-α lead to increased formation of RANKL and decreased production of OPG resulting in bone lost. [38394041]…”