Effect of technetium‐99 conjugated with methylene diphosphonate (⁹⁹Tc‐MDP) on OPG/RANKL/RANK system in vitro

Abstract

Background RANKL and RANK play an important role in jaw resorption during the development of the ameloblastomas. Therefore, the aim of this study was to explore the effect of 99Tc‑MDP on OPG/RANKL/RANK system on RAW264.7 and MC3T3‐E1 cell lines in vitro and provide the theoretical basis for the clinical treatment of the jaw ameloblastoma. Methods Different concentrations of 99Tc‐MDP were used to treat RAW264.7 and MC3T3‐E1 cell lines. The cell proliferative inhibition rate was analyzed by CCK‐8. Cell apoptosis and cell cycle were detected by flow cytometry. Western blot was used to detect the expression of OPG, RANKL, and RANK. Results Treatment of RAW264.7 cell lines with different concentrations of 99Tc‐MDP had inhibitory effects and decreased the expression of RANK protein. The cell proliferation of 99Tc‐MDP on MC3T3‐E1 cell lines was stronger at 48 hours than at 24 hours except for 100 μg/mL concentration group. Compared with the concentration of 0.01 μg/mL, the treatment of MC3T3‐E1 cells with 100 μg/mL 99Tc‐MDP showed that the cell proliferative effect decreased at 24 hours and 48 hours (P < 0.05). After treatment with 0.01 μg/mL 99Tc‐MDP, the expression of OPG in MC3T3‐E1 cells was significantly increased (P < 0.05). Compared with 0.01 μg/mL, the expression of RANKL was decreased after treatment with 100 μg/mL 99Tc‐MDP (P < 0.05). Conclusion 99Tc‐MDP can induce apoptosis of RAW264.7 cells and inhibit the expression of RANK protein. The effect of 0.01 μg/mL of low concentration of 99Tc‐MDP can promote the proliferation of MC3T3‐E1 cells and increase the expression of OPG and RANKL protein. 99Tc‐MDP may have adjuvant therapeutic effects on the treatment of jaw ameloblastoma.

Effectiveness and safety of 99Tc-methylene diphosphonate as a disease-modifying anti-rheumatic drug (DMARD) in combination with conventional synthetic (cs) DMARDs in the treatment of rheumatoid arthritis: A systematic review and meta-analysis of 34 randomized controlled trials

“…99Tc-MDP induces the differentiation of osteoblasts by significantly increasing the expression of bone morphogenetic protein-2 (BMP-2) and alkaline phosphatase (ALP) in vitro [ 7 ]. In addition, 99Tc-MDP regulates the osteoprotegerin/receptor activator of nuclear factor-kappaB and its ligand (OPG/RANK/RANKL) system, and inhibit OCs mediated bone resorption [ 50 , 51 ]. MDP is a new type of bisphosphonate, and bisphosphonates are considered the most classic drugs for combating osteoporosis [ 52 ].…”

Cucumber seed polypeptides regulate RANKL-induced osteoclastogenesis through OPG/RANKL/RANK and NF-κB

“…Dimethylbisphosphonate plus 99Tc-MDP can induce apoptosis in RAW264.7 cells by regulating the OPG/RANKL/RANK pathway, inhibiting RANK protein expression, and promoting MC3T3-E1 cell proliferation (Shen et al . 2019 ). Chen et al .…”