Genipin and insulin combined treatment improves implant osseointegration in type 2 diabetic rats

Abstract

Background Type 2 diabetes mellitus (T2DM) has a harmful effect on the stability and osseointegration of dental implants. T2DM induces mitochondrial damage by inhibiting AMPK signaling, resulting in oxidative stress and poor osteogenesis in the peri-implant bone area. Genipin is a major component of gardenia fruits with strong antioxidant, anti-inflammation, and antidiabetic actions, and it also can activate mitochondrial quality control via the AMPK pathway. The purpose of this study was to investigate the effects of genipin and insulin treatment on implant osseointegration in T2DM rats and explore the underlying mechanisms. Methods Streptozotocin-induced diabetic rats received implant surgery in their femurs and were then assigned to five groups that were subjected to different treatments for three months: control group, T2DM group, insulin-treated T2DM group (10 IU/kg), genipin-treated T2DM group (50 mg/kg), and the genipin and insulin combination-treated T2DM group. Then, we regularly assessed the weight and glucose levels of the animals. Rats were euthanized at 3 months after the implantation procedure, and the femora were harvested for microscopic computerized tomography analysis, biomechanical tests, and different histomorphometric assessment. Results The results indicated that the highest blood glucose and oxidative stress levels were measured for the T2DM group, resulting in the poorest osseointegration. The combination-treated T2DM group mitigated hyperglycemia and normalized, reactivated AMPK signaling, and alleviated oxidative stress as well as reversed the negative effect of osseointegration. There were beneficial changes observed in the T2DM-genipin and T2DM-insulin groups, but these were less in comparison to the combination treatment group. Conclusion Our study suggests that treatment with genipin in combination with insulin could be an effective method for promoting implant osseointegration in T2DM rats, which may be related to AMPK signaling.

Specific RNA m6A modification sites in bone marrow mesenchymal stem cells from the jawbone marrow of type 2 diabetes patients with dental implant failure

“…Adiponectin, a cytokine, could also improve the osteointegration of implants by rescuing mitochondrial impaired through the AMPK pathway under diabetic conditions, both in vivo and in vitro. 5 , 66 Selenomethionine, a naturally occurring amino acid-containing selenium, could attenuate H 2 O 2 -induced suppression of the osteogenic differentiation of BMSCs through an antioxidant effect that was modulated by PTEN/PI3K/AKT pathway, which could be a promising antioxidant candidate by which to reduce oxidative stress during dental implant osteointegration process. 67 Our study, in combination with previous studies, showed that ADNP and GDF11 may affect the metabolic process and antioxidant functions of DM-BMSCs, which could thus be a crucial target by which to address implant stability and bone integration in patients with T2DM.…”

“… 4 A previous study also reported that insulin-treated T2DM rats had improved bone regeneration and trabecular microstructure to some extent, but not comparable to the control group. 5 Furthermore, a recent clinical study discovered that T2DM patients with good glycaemic control had lower implant stability during the healing stage than patients without diabetes. 6 It is thus clear that we need to improve our knowledge regarding the key factors that affect implant failure in patients with diabetes in order to improve the success rate of implantation.…”

Microemulsion Delivery System Improves Cellular Uptake of Genipin and Its Protective Effect against Aβ1-42-Induced PC12 Cell Cytotoxicity

“…Recently, multiple pharmacological activities of geniposide and its aglycone genipin have been reported, including its hepatoprotective effect [ 3 ], hypoglycemic [ 4 ] and anti-inflammatory activity [ 5 ], protection of cerebral ischemic injury [ 6 ], neuroprotection [ 7 ], and anti-depressant effects [ 8 ]. Although geniposide has been widely considered as the main active component, some studies suggested that genipin was a more active ingredient [ 9 , 10 , 11 ].…”

Genipin protects against mitochondrial damage of the retinal pigment epithelium under hyperglycemia through the AKT pathway mediated by the miR-4429/JAK2 signaling axis

“…Genipin (GE) has been shown to be an effective treatment for retinal pigment epithelium injury through the development of diabetes drugs (9). Derived from the extraction and purification of gardenia jasminoides, GE has effective anti-inflammatory, antioxidant, and anti-diabetes properties (10).…”