ED-71 promotes osseointegration of titanium implants in a rat model of GIOP by alleviating the effects of dexamethasone on bone remodeling in a SIRT1-dependent manner

  • J Oral Biosci. 2024 Oct 10:S1349-0079(24)00205-6. doi: 10.1016/j.job.2024.10.003.
Chunying Li  1 ,  Pengfei Xue  2 ,  Guanglin Duan  3 ,  Ailing Song  3 ,  Runbing Zhai  3 ,  Jie Ma  3 ,  Minqi Li  4
Affiliations
  • 1. Department of stomatology, Zibo Municipal Hospital, Zibo, China; Center of Osteoporosis and Bone Mineral Research, Shandong University, Jinan, China. Electronic address: [email protected].
  • 2. Department of stomatology, Zibo Municipal Hospital, Zibo, China; Center of Osteoporosis and Bone Mineral Research, Shandong University, Jinan, China.
  • 3. Department of stomatology, Zibo Municipal Hospital, Zibo, China.
  • 4. Center of Osteoporosis and Bone Mineral Research, Shandong University, Jinan, China.
PMID: 39395651 DOI: 10.1016/j.job.2024.10.003
Abstract

Objective: Glucocorticoid-induced osteoporosis (GIOP), a common complication of glucocorticoid usage, plays a critical role in the success of dental implant restoration by affecting osseointegration. Eldecalcitol (ED-71) prevents GIOP; however, its role in the osseointegration of implants under GIOP conditions remains elusive.

Methods: Dexamethasone was used to establish a rat model of GIOP. Subsequently, mini-implant surgery was performed on the femur. GIOP rats were administered ED-71 via gavage to assess its role in the osseointegration of titanium implants under GIOP conditions. MC3T3-E1 and RAW264.7 cells were utilized to explore the molecular mechanism of ED-71 in ameliorating disorder of bone remodeling caused by dexamethasone.

Results: The administration of ED-71 promoted the formation of newly formed woven bone and the resolution of inflammation around titanium implants. In vitro experiments indicated that ED-71 ameliorated dexamethasone-induced dysfunction of osteoblasts and osteoclasts by increasing the expression level of Sirtuin 1 (SIRT1). Inhibition of SIRT1 by selisistat counteracts the regulatory effects of ED-71 on dexamethasone-induced disorder of bone remodeling. Molecular docking and Western blotting revealed that the neurogenic locus Notch homolog protein and nuclear factor kappa B signaling pathways are essential for the effects of ED-71 on dexamethasone-induced disorder of bone remodeling.

Conclusion: ED-71 promoted implant osseointegration in a rat model of GIOP by alleviating the effects of dexamethasone on bone remodeling in a SIRT1-dependent manner.

Keywords
ED-71; GIOP; SIRT1; osseointegration of implants.
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