Role of interaction between reactive oxygen species and ferroptosis pathway in methylglyoxal-induced injury in mouse embryonic osteoblasts / 南方医科大学学报

OBJECTIVE@#To explore the interaction between reactive oxygen species (ROS) and ferroptosis in methylglyoxalinduced injury of mouse embryonic osteoblasts (MC3T3-E1 cells).@*METHODS@#MC3T3-E1 cells were treated with methylglyoxal to establish a cell model of diabetic osteoporosis. CCK-8 assay was used to detect the viability of MC3T3-E1 cells. Rhodamine 123 staining followed by photofluorography was used to examine mitochondrial membrane potential (MMP). The intracellular ROS level was detected by 2', 7'-dichlorodihydrofluorescein diacetate staining with photofluorograph. Alkaline phosphatase (ALP) activity in the cells was detected using an ALP kit, the number of mineralized nodules was determined with alizarin red S staining, and the level of iron ions was detected using a detection kit. The expression level of glutathione peroxidase 4 (GPX4, a marker protein that inhibits ferroptosis) in the osteoblasts was determined using Western blotting.@*RESULTS@#Treatment of MC3T3-E1 cells with 0.6 mmol/L methylglyoxal for 24 h significantly inhibited the expression level of GPX4 (P < 0.001), increased intracellular iron ion concentration, decreased the cell viability, increased the loss of MMP and intracellular ROS level, decreased both ALP activity and the number of mineralized nodules in the cells (P < 0.001). Co-treatment of MC3T3-E1 cells with 2 mmol/L N-acetylcysteine (NAC, a ROS scavenger) and methylglyoxal significantly increased the expression level of GPX4 (P < 0.01); co-treatment with 4 mmo/L FER-1 (a ferroptosis inhibitor) and methylglyoxal obviously decreased the intracellular ROS level (P < 0.001). Co-treatment of the cells either with NAC and methylglyoxal or with FER-1 and methylglyoxal attenuated methylglyoxal-induced injuries in the osteoblasts (P < 0.001).@*CONCLUSION@#The interaction between ROS and ferroptosis pathway plays an important role in methylglyoxal-induced injury of mouse embryonic osteoblasts.

Factors associated with acute febrile reaction in elderly patients receiving intravenous zoledronic acid for osteoporosis / 南方医科大学学报

<p><b>OBJECTIVE</b>To survey the incidence of acute febrile reaction in elderly patients receiving intravenous zoledronic acid for osteoporosis and identify the related factors.</p><p><b>METHODS</b>Thirty-eight elderly patients with osteoporosis were hospitalized and treated with intravenous infusion of 5 mg zoledronic acid in 2010. The incidence of acute fever reaction was observed in these patients , and the time of fever onset, duration, average maximum temperature, and antipyretic drug used were recorded. The patients with and without acute febrile reaction were compared for age, duration of osteoporosis, sex ratio, use of parathyroid hormone before zoledronic acid treatment, β-fragment of collagen breakdown, calcitonin, osteocalcin, serum calcium, and use of anti-osteoporosis drugs before the treatment.</p><p><b>RESULTS</b>Acute fever reaction occurred in 12 (31.6%) of the patients. Two of the patients had fever on the day of zoledronic acid treatment, and the other patients developed fever after the first day of treatment, with a mean duration of 1 day and a maximum temperature of (38.5∓0.84) degrees celsius;. The fever was treated with a mean of 3.55∓1.21 pseudoephedrine tablets. The patients with fever showed significantly higher parathyroid hormone levels before treatment than those without fever (P<0.05); osteocalcin, calcitonin, β-fragment of collagen breakdown, or serum calcium showed no significant difference between the two groups.</p><p><b>CONCLUSION</b>Acute febrile reaction, often moderate and transient, is common in elderly patients receiving intravenous zoledronic acid for osteoporosis, and its occurrence is possibly associated with parathyroid hormone levels before the treatment.</p>