CpG ODN/Mangiferin Dual Delivery through Calcium Alginate Hydrogels Inhibits Immune-Mediated Osteoclastogenesis and Promotes Alveolar Bone Regeneration in Mice
机构：[1]Department of Immunology and Infectious Diseases, The Forsyth Institute, 245 First Street, Cambridge, MA 02142, USA.[2]Department of Orthodontics, Beijing Stomatological Hospital, Capital Medical University, Beijing 100050, China.[3]Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University, Fort Lauderdale, FL 33314, USA.[4]Department of Stomatology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China.临床科室口腔科首都医科大学附属北京同仁医院首都医科大学附属同仁医院
The immune system plays an important role in the skeletal system during bone repair and regeneration. The controlled release of biological factors from the immune system could facilitate and optimize the bone remodeling process through the regulation of the activities of bone cells. This study aimed to determine the effect of the controlled delivery of immunomodulatory biologicals on bone regeneration. Immunostimulatory cytosine-phosphate-guanosine oligodeoxynucleotides (CpG ODN) and glucosylxanthone Mangiferin (MAG)-embedded microbeads were incubated with P. gingivalis-challenged splenocytes, or co-cultured with RAW264.7 cells. The effect of CpG ODN/MAG-containing microbeads on bone regeneration was then tested in vivo in a mouse alveolar bone defect model. The results demonstrated that MAG significantly antagonized P. gingivalis proliferation and reduced the live/dead cell ratio. After the addition of CpG ODN + MAG microbeads, anti-inflammatory cytokines IL-10 and IL-4 were upregulated on day 2 but not day 4, whereas pro-inflammatory cytokine IL-1β responses showed no difference at both timepoints. RANKL production by splenocytes and TRAP+ cell formation of RAW264.7 cells were inhibited by the addition of CpG ODN + MAG microbeads. Alveolar bony defects, filled with CpG ODN + MAG microbeads, showed significantly increased new bone after 4 weeks. In summary, this study evaluated a new hydrogel-based regimen for the local delivery and controlled release of biologicals to repair and regenerate alveolar bony defects. The combined CpG ODN + MAG treatment may promote alveolar bone regeneration through the anti-microbial/anti-inflammatory effects and the inhibition of RANKL-mediated osteoclastogenesis.
基金：
This research was funded by the National Institutes of Health (NIH) grant number
R01DE025255 to X.H., DE027851 to T.K., DE028715 to T.K., and DE029709 to T.K. Forsyth Pilot
grant FPILOT 60 to X.H. The APC was funded by NIH.
第一作者机构：[1]Department of Immunology and Infectious Diseases, The Forsyth Institute, 245 First Street, Cambridge, MA 02142, USA.[2]Department of Orthodontics, Beijing Stomatological Hospital, Capital Medical University, Beijing 100050, China.
通讯作者：
通讯机构：[1]Department of Immunology and Infectious Diseases, The Forsyth Institute, 245 First Street, Cambridge, MA 02142, USA.[3]Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University, Fort Lauderdale, FL 33314, USA.
推荐引用方式(GB/T 7714)：
Gu Yingzhi,Hu Yang,Huang Shengyuan,et al.CpG ODN/Mangiferin Dual Delivery through Calcium Alginate Hydrogels Inhibits Immune-Mediated Osteoclastogenesis and Promotes Alveolar Bone Regeneration in Mice[J].BIOLOGY-BASEL.2023,12(7):doi:10.3390/biology12070976.
APA：
Gu Yingzhi,Hu Yang,Huang Shengyuan,Ruiz Sunniva,Kawai Toshihisa...&Han Xiaozhe.(2023).CpG ODN/Mangiferin Dual Delivery through Calcium Alginate Hydrogels Inhibits Immune-Mediated Osteoclastogenesis and Promotes Alveolar Bone Regeneration in Mice.BIOLOGY-BASEL,12,(7)
MLA：
Gu Yingzhi,et al."CpG ODN/Mangiferin Dual Delivery through Calcium Alginate Hydrogels Inhibits Immune-Mediated Osteoclastogenesis and Promotes Alveolar Bone Regeneration in Mice".BIOLOGY-BASEL 12..7(2023)
