Zoledronate Promotes Peri-Implant Osteogenesis in Diabetic Osteoporosis by the AMPK Pathway.

Together with diabetic osteoporosis (DOP), diabetes patients experience poor peri-implant osteogenesis following implantation for dentition defects. Zoledronate (ZOL) is widely used to treat osteoporosis clinically. To evaluate the mechanism of ZOL for the treatment of DOP, experiments with DOP rats and high glucose-grown MC3T3-E1 cells were used. The DOP rats treated with ZOL and/or ZOL implants underwent a 4-week implant-healing interval, and then microcomputed tomography, biomechanical testing, and immunohistochemical staining were performed to elucidate the mechanism. In addition, MC3T3-E1 cells were maintained in an osteogenic medium with or without ZOL to confirm the mechanism. The cell migration, cellular actin content, and osteogenic differentiation were evaluated by a cell activity assay, a cell migration assay, as well as alkaline phosphatase, alizarin red S, and immunofluorescence staining. The mRNA and protein expression of adenosine monophosphate-activated protein kinase (AMPK), phosphorylated AMPK (p-AMPK), osteoprotegerin (OPG), receptor activator of nuclear factor kappa B ligand (RANKL), bone morphogenetic protein 2 (BMP2), and collagen type I (Col-I) were detected using real-time quantitative PCRs and western blot assays, respectively. In the DOP rats, ZOL markedly improved osteogenesis, enhanced bone strength and increased the expression of AMPK, p-AMPK, and Col-I in peri-implant bones. The in vitro findings showed that ZOL reversed the high glucose-induced inhibition of osteogenesis via the AMPK signaling pathway. In conclusion, the ability of ZOL to promote osteogenesis in DOP by targeting AMPK signaling suggests that therapy with ZOL, particularly simultaneous local and systemic administration, may be a unique approach for future implant repair in diabetes patients.

Antibacterial and Antioxidant Effects of Magnesium Alloy on Titanium Dental Implants.

OBJECTIVES: In this study, a new type of dental implant by covering the surface of the titanium (Ti) implant with zinc-magnesium (Zn-Mg) alloy was designed, to study the antibacterial and antioxidant effects of Mg alloy on titanium (Ti) implants in oral implant restoration. METHODS: Human gingival fibroblasts (HGFs), S. sanguinis, and F. nucleatum bacteria were used to detect the bioactivity and antibacterial properties of Mg alloy-coated Ti implants. In addition, B6/J mice implanted with different materials were used to further detect their antibacterial and antioxidant properties. RESULTS: The results showed that Mg alloy could better promote the adhesion and proliferation and improve the alkaline phosphatase (ALP) activity of HGFs, which contributed to better improved stability of implant osseointegration. In addition, Mg alloy could better inhibit the proliferation of S. sanguinis, while no significant difference was found in the proliferation of F. nucleatum between the two implants. In the mouse model, the peripheral inflammatory reaction and oxidative stress of the Mg alloy implant were significantly lower than those of the Ti alloy implant. CONCLUSIONS: Zn-Mg alloy-coated Ti implants could better inhibit the growth of Gram-positive bacteria in the oral cavity, inhibit oxidative stress, and facilitate the proliferation activity of HGFs and the potential of osteoblast differentiation, thus, better increasing the stability of implant osseointegration.

[Zoledronate regulates osteoclast differentiation and bone resorption in high glucose through p38 MAPK pathway].

OBJECTIVE: To investigate the effect of zoledronate (ZOL) on osteoclast differentiation and bone resorption under high glucose, and the regulation mechanism of p38 mitogen activated kinase (p38 MAPK) signaling pathway in this process. METHODS: RAW264.7 cells were divided into four groups: low group, high group, low+ZOL group and high+ZOL group after induced into osteoclasts. Cell proliferation activity was determined by MTT assay. The migration of RAW264.7 cells were examined Optical microscopy. Immunofluorescence microscopy was used to observe the cytoskeleton and sealing zones of osteoclasts. After adding group 5: high + ZOL + SB203580 group, trap staining was used to identify the number of positive osteoclasts in each group. The number and area of resorption lacunae were observed by SEM. The mRNA and protein expression of osteoclast related factors were detected by real-time PCR and Western blotting. RESULTS: The cells in the 5 groups showed similar proliferative activity. High glucose promoted the migration of RAW264.7 cells (P < 0.05), inhibited the clarity of cytoskeleton and the formation of sealing zones in the osteoclasts. Exposure to high glucose significantly lowered the expressions of p38 MAPK, p-p38 MAPK, NFATc1, CTSK and TRAP, and inhibited osteoclast differentiation and bone absorption (P < 0.05). Treatment with ZOL obviously suppressed the migration ability of RAW264.7 cells, further reduced the clarity of the cytoskeleton, inhibited the formation of sealing zones of the osteoclasts, lowered the expressions of p38 MAPK, p-p38 MAPK, NFATc1, CTSK, and TRAP (P < 0.05), and inhibited osteoclast differentiation and bone absorption. Treatment with SB203580 obviously inhibited osteoclast differentiation and bone resorption and the expressions of P38 MAPK, p-p38 MAPK, NFATc1, CTSK and TRAP (P < 0.05). CONCLUSIONS: High glucose inhibits osteoclast differentiation and bone resorption. ZOL inhibits osteoclast differentiation and bone resorption in high-glucose conditions by regulating p38 MAPK pathway, which can be a new pathway for ZOL to regulate diabetic osteoporosis.