Molecular Regulation of Bone Metastasis Pathogenesis

Distant metastases are the major cause of mortality in cancer patients. Bone metastases may cause bone fractures, local pain, hypercalcemia, bone marrow aplasia, and spinal cord compression. Therefore, the management of bone metastases is important in cancer treatment. Normal bone remodeling is regulated by osteoprotegerin ligand (OPGL), receptor activator of NF-κB ligand (RANKL), parathyroid hormone-related protein (PTHrP), and other cytokines. In the tumor microenvironment, tumor cells induce a vicious cycle that promotes osteoblastic and osteolytic lesions. Studies support the idea that distant metastases may occur due to the immunosuppressive function of myeloid-derived suppressor cells (MDSCs). These cells inhibit T cells and natural killer (NK) cells and differentiate into tumor-associating macrophages (TAMs), monocytes, and dendritic cells (DCs). In this review, we summarize studies focusing on the role of MDSCs in bone metastasis and provide a strong foundation for developing anticancer immune treatments and anticancer therapies, in general.

Effects of Electroacupuncture on Bone Mineral Density, Oestradiol Level and Osteoprotegerin Ligand Expression in Ovariectomised Rabbits

Objectives To investigate the effects of electroacupuncture (EA) on the oestradiol level, bone mineral density and osteoprotegerin ligand (OPGL) expression, and to explore whether EA might be a complementary method to prevent and treat osteoporosis. Methods A total of 21 New Zealand rabbits were randomly divided into three groups: a normal control (NC) group undergoing no surgery or EA; an ovariectomised (OVX) group, in which rabbits were ovariectomised but did not receive EA; an EA group, in which rabbits were ovariectomised and treated with EA. Acupuncture was applied at ST35, BL20 and BL23 points bilaterally. EA (10 Hz, 2 mA) was applied bilaterally at BL20 and BL23 for 30 min a day for 14 days. After 14 days, all animals were killed. OPGL expression level was determined by immunohistochemistry. Blood serum levels of oestradiol were measured by ELISA and bone mineral density was detected by dual-energy x-ray absorptiometry. Results After ovariectomy, the bone mineral density and oestradiol level decreased significantly in the OVX group compared with the NC group (p=0.001), whereas the OPGL expression level increased. After EA, the bone mineral density and oestradiol level increased compared with the OVX group (p=0.049 and p=0.012, respectively). The OPGL level OPGL level in the EA group was lower than that in the OVX group (p=0.022). Conclusions EA restored bone mineral density towards normal and was associated with increased plasma oestradiol level and reduced OPGL expression in an ovariectomised rabbit model of osteoporosis.

Mixed Periodontal Th1-Th2 Cytokine Profile in Actinobacillus actinomycetemcomitans-Specific Osteoprotegerin Ligand (or RANK-L)- Mediated Alveolar Bone Destruction In Vivo

ABSTRACT The Th1/Th2 cytokines involved in human periodontitis remain unclear; therefore, we established a humanized mouse model to investigate this issue in Actinobacillus actinomycetemcomitans-mediated periodontal infection. Quantitative-PCR analysis clearly demonstrates a predominantly mixed Th1 and Th2 expression profile associated with pathogen-specific cell-mediated immunity via osteoprotegerin ligand (or RANK-L)-mediated alveolar bone destruction in vivo.