Celastrol Attenuates RANKL-Induced Osteoclastogenesis in vitro and Reduces Titanium Particle-Induced Osteolysis and Ovariectomy-Induced Bone Loss in vivo

Abstract

Excessive bone resorption by osteoclasts contributes significantly to osteoclast-related diseases such as periprosthetic osteolysis and osteoporosis. Osteolysis in a titanium particle-induced calvarial model and bone loss in an ovariectomized mice model occurred similarly to those in humans; thus, these models can be used to evaluate potential therapies for aseptic prosthetic loosening and osteoporosis. Celastrol, which is extracted from the seeds of the genus Tripterygium, has been thoroughly investigated for its anti-inflammatory and anti-cancer pharmacological effects. However, the mechanisms involving bone metabolism by which celastrol inhibits osteoclastogenesis are not yet fully understood. We demonstrated that celastrol inhibited the receptor activator of nuclear factor κB ligand-induced osteoclastogenesis and the bone resorptive function of osteoclasts in vitro by inhibiting the activation of transforming growth factor β-activated kinase 1-mediated NF-κB and mitogen-activated protein kinase signaling pathways and downregulating osteoclastogenesis marker-related genes. Furthermore, celastrol was also shown to be beneficial in both the titanium particle-induced osteolysis calvarial and the murine ovariectomy-induced bone loss. Collectively, our results suggested that celastrol is promising for the prevention of aseptic prosthetic loosening and osteoporosis in the treatment of osteolytic diseases induced by disrupted osteoclast formation and function.

Acacetin Prevents Bone Loss by Disrupting Osteoclast Formation and Promoting Type H Vessel Formation in Ovariectomy-Induced Osteoporosis

“…Osteoporosis is a common bone disease characterized by excessive bone resorption mediated by osteoclasts and resulting in bone loss ( Qiang Xu et al, 2021 ). It is estimated that more than 200 million people currently suffer from osteoporosis ( Tatangelo et al, 2019 ).…”

“…Osteoporosis is a chronic bone disease characterized by destruction of bone microstructure and low bone mass, leading to increased bone fragility and thus increased fracture susceptibility ( Chujiao Lin et al, 2019 ). Bone resorption mediated by osteoclasts exceeds bone formation mediated by osteoblasts, which is one of the potential mechanisms of osteoporosis ( Qiang Xu et al, 2021 ). Studies have shown that 50% of women will suffer fractures due to osteoporosis in their lifetimes ( Beekman et al, 2019 ).…”

Gallic acid inhibits osteoclastogenesis and prevents ovariectomy-induced bone loss

“…Since excessive activation of OC plays a dominant role in bone loss, the development of new drugs to inhibit OC differentiation is a major and promising target for the treatment of osteoporosis ( 20 , 21 ). However, the clinical antiresorptive agents for osteoporosis are accompanied by several side effects, including osteonecrosis of the jaw, gastrointestinal discomfort, and hypokalaemia ( 22 ), new therapeutic strategies to prevent osteoporosis are urgently needed.…”

Exploration of the effect of Celastrol on protein targets in nasopharyngeal carcinoma: Network pharmacology, molecular docking and experimental evaluations

“…It is also important to note that female mice were used for animal experiments in this study, and although the experimental animals were not deliberately selected in terms of sex, this may have biased the experimental results in some ways. Moreover, the sample size of the experimental animals was only referred to other literature ( Li et al, 2018 ; Xu et al, 2021 ) without detailed calculation. Therefore these issues need to be taken into account in future studies.…”