Monocrotaline Suppresses RANKL-Induced Osteoclastogenesis In Vitro and Prevents LPS-Induced Bone Loss In Vivo

Abstract

Background/Aims: Extensive osteoclast formation plays a critical role in bone diseases, including rheumatoid arthritis, periodontitis and the aseptic loosening of orthopedic implants. Thus, identification of agents that can suppress osteoclast formation and bone resorption is important for the treatment of these diseases. Monocrotaline (Mon), the major bioactive component of crotalaria sessiliflora has been investigated for its anti-cancer activities. However, the effect of Mon on osteoclast formation and osteolysis is not known. Methods: The bone marrow macrophages (BMMs) were cultured with M-CSF and RANKL followed by Mon treatment. Then the effects of Mon on osteoclast differentiation were evaluated by counting TRAP (+) multinucleated cells. Moreover, effects of Mon on hydroxyapatite resorption activity of mature osteoclast were studied through resorption areas measurement. The involved potential signaling pathways were analyzed by performed Western blotting and quantitative real-time PCR examination. Further, we established a mouse calvarial osteolysis model to measure the osteolysis suppressing effect of Mon in vivo. Results: In this study, we show that Mon can inhibit RANKL-induced osteoclast formation and function in a dose-dependent manner. Mon inhibits the expression of osteoclast marker genes such as tartrate-resistant acid phosphatase (TRAP) and cathepsin K. Furthermore, Mon inhibits RANKL-induced the activation of p38 and JNK. Consistent with in vitro results, Mon exhibits protective effects in an in vivo mouse model of LPS-induced calvarial osteolysis. Conclusion: Taken together our data demonstrate that Mon may be a potential prophylactic anti-osteoclastic agent for the treatment of osteolytic diseases caused by excessive osteoclast formation and function.

Retracted: Daidzin inhibits RANKL‐induced osteoclastogenesis in vitro and prevents LPS‐induced bone loss in vivo

“…[4][5][6]15 Currently, the major modalities used in these diseases treatment, including bisphosphonates, 27 denosumab, 28 and selective estrogen receptor modulators. [4][5][6]15 Currently, the major modalities used in these diseases treatment, including bisphosphonates, 27 denosumab, 28 and selective estrogen receptor modulators.…”

“…8,9 M-CSF stimulates osteoclast proliferation, whereas RANKL is important for the formation of multinuclear giant osteoclasts. 15 Nowadays, many studies have indicated that several compounds derived from natural products promote bone formation by advancing osteoblast differentiation and suppressing the signal pathways for osteoclast formation. Then, TRAF6 stimulates downstream signaling pathways, such as NF-κB signaling pathways.…”

Diosmetin inhibits osteoclast formation and differentiation and prevents LPS‐induced osteolysis in mice

“…After micro-CT analyses, the calvarias samples were decalcified for 2 weeks in 10% EDTA. Then, paraffin-embedded histopathological sections were used for TRAcP staining, hematoxylin and eosin (H&E) staining, and immunohistochemical staining as previously described (Song et al, 2017;Wei et al, 2018). The TRAcP-positive osteoclasts were determined by ImageJ software.…”

Vaccarin prevents titanium particle‐induced osteolysis and inhibits RANKL‐induced osteoclastogenesis by blocking NF‐κB and MAPK signaling pathways

“…OCs are the only cells in the human body that undergo bone resorption; inhibiting their differentiation and formation can effectively inhibit bone loss and bone dissolution (Wei, Su, et al, ). The results of the experiments carried out in this study demonstrated that Vac could inhibit the differentiation and formation of OCs in a dose‐dependent manner.…”