Int J Stomatol ›› 2020, Vol. 47 ›› Issue (5): 538-546.doi: 10.7518/gjkq.2020086

• Original Articles • Previous Articles     Next Articles

Preliminary study on osteoprotegerin/receptor activator of nuclear factor-κB ligand expression in mandible and femur on site selectivity of bone metastasis of lung cancer cells

Fu Shijin(),Zeng Kan,Li Xin,Yang Jing,Wang Chenglin,Ye Ling()   

  1. State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Dept. of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
  • Received:2020-01-10 Revised:2020-05-11 Online:2020-09-01 Published:2020-09-16
  • Contact: Ling Ye;
  • Supported by:
    National Natural Science Foundation of China for Distinguished Young Scholars(81825005)


Objective To explore the involvement of osteoprotegerin (OPG)/receptor activator of nuclear factor-κB ligand (RANKL) ratio in mandible and femur on the site selectivity of bone metastasis of lung cancer cells. Methods Mouse Lewis lung cancer cells were used to construct mouse models of systemic/local lung cancer bone metastasis. Hematoxylin-eosin staining and micro-computed tomography (MicroCT) analysis were used to determine the selectivity of tumor metastasis amongst different bone tissues. Immunohistochemical staining of cathepsin K (CTSK) was performed to detect osteoclast activation in bone tissues. RNA sequencing (RNA-seq) and real time-quantitative polymerase chain reaction (RT-qPCR) were conducted to measure OPG mRNA/RANKL mRNA in bone.Results Using the mouse model of systemic lung-cancer cell bone metastasis, we established that the bone metastasis was less likely to occur in the mandible than the femur. Under physiological conditions, taking the mandible and femur as representative bone tissues with low/high incidence of lung cancer-cell metastasis, we found that the mandible exhibited a significantly fewer osteoclast number and higher OPG mRNA/RANKL mRNA ratio than the femur (P<0.01). Further investigations suggested that lung cancer cell-induced bone destruction mainly distributed in areas concentrated with CTSK-positive osteoclasts, with a significantly greater osteoclast number (P<0.01) and lower OPG mRNA/RANKL mRNA ratio in the metastasized bone tissue compared with the non-metastasized bone tissue (P<0.000 1). Conclusion Differences in osteoclast activation and OPG mRNA/RANKL mRNA ratio levels exist in bone tissues with low/high incidence of lung cancer-cell bone metastasis, suggesting that OPG/RANKL may affect osteoclast activation, and is therefore involved in the site selectivity of lung cancer-cell bone metastasis.

Key words: lung cancer cells bone metastasis, mandible, femur, osteoclast, osteoprotegerin, receptor activator of nuclear factor-κB ligand

CLC Number: 

  • Q257


Fig 1

Lung metastasis in mice by injection of LLC cells through tail vein"

Fig 2

Tumor colonization and bone destruction occurred in mandible and femur in mouse model of systemic lung cancer cells bone metastasis"

Fig 3

Analysis of cathepsin K-positive osteoclasts in normal physiological mandible and femur"

Fig 4

Analysis of OPG mRNA/RANKL mRNA ratios in normal physiological mandible and femur"

Fig 5

Osteoclasts activation and OPG mRNA/RANKL mRNA ratios in bone tissues of the experimental and conrtrol groups"

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