Aims. This study was performed to explore the effect of melatonin on pyroptosis in nucleus pulposus cells (NPCs) and the underlying mechanism of that effect. Methods. This experiment included three patients diagnosed with lumbar disc herniation who failed conservative treatment. Nucleus pulposus tissue was isolated from these patients when they underwent surgical intervention, and primary NPCs were isolated and cultured. Western blotting, reverse transcription polymerase chain reaction, fluorescence staining, and other methods were used to detect changes in related signalling pathways and the ability of cells to resist pyroptosis. Results. Western blot analysis confirmed the expression of cleaved CASP-1 and melatonin receptor (MT-1A-R) in NPCs. The cultured NPCs were identified by detecting the expression of CD24, collagen type II, and aggrecan. After treatment with hydrogen peroxide, the pyroptosis-related proteins NLR family pyrin domain containing 3 (NLRP3), cleaved CASP-1, N-terminal fragment of gasdermin D (GSDMD-N), interleukin (IL)-18, and IL-1β in NPCs were upregulated, and the number of propidium iodide (PI)-positive cells was also increased, which was able to be alleviated by pretreatment with melatonin. The protective effect of melatonin on pyroptosis was blunted by both the melatonin receptor antagonist luzindole and the nuclear factor erythroid 2–related factor 2 (Nrf2) inhibitor ML385. In addition, the expression of the transcription factor Nrf2 was up- or downregulated when the melatonin receptor was activated or blocked by melatonin or luzindole, respectively. Conclusion. Melatonin protects NPCs against reactive oxygen species-induced pyroptosis by upregulating the transcription factor Nrf2 via melatonin receptors. Cite this article: Bone Joint Res 2023;12(3):202–211

The scoliosis observed in chickens after pinealectomy resembles that seen in humans with an adolescent idiopathic scoliosis, suggesting that melatonin deficiency may be responsible. However, to date there have been no studies of pineal gland glucose metabolism in patients with adolescent idiopathic scoliosis that might support this hypothesis. We examined the excretion of urinary 6-sulfatoxyl-melatonin as well as the glucose metabolism of the pineal gland in 14 patients with an adolescent idiopathic scoliosis and compared them with those of 13 gender-matched healthy controls using F-18 fluorodeoxyglucose brain positron emission tomography. There was no significant difference in the level of urinary 6-sulfatoxyl-melatonin or pineal gland metabolism between the study and the control group. We conclude that permanent melatonin deficiency is not a causative factor in the aetiology of adolescent idiopathic scoliosis

Introduction. Melatonin-deficient rats are known to develop scoliosis when rendered bipedal. In a previous study we have shown that melatonin-deficient bipedal mice with scoliosis had lower bone density than did mice without scoliosis. Published work suggests that children with AIS have lower bone density than do healthy children. The aim of this study is to establish whether osteoporosis causes scoliosis. We hypothesised that bipedal rats with lower bone density would have increased spinal malalignment compared with the control group. Methods. 50 female Sprague-Dawley rats were rendered bipedal at 3 weeks of age by amputation of the forelimbs and tails. Two groups were formed: control group (n=25), in which rats received no drug; and the experiment group (n=25), in which rats received daily subcutaneous 1 U/g heparin injections. Animals were kept in standard cages, and food and water was provided at the top of the cages to encourage more time standing erect. DEXA scans were done on week 4 to assess bone density. Radiographs were taken on week 40 to assess spinal alignment in both control and experiment groups. Results. 19 rats in the heparin group and 23 rats in the control group were available for evaluation at the end of the study. At week 4, DEXA scans showed significant difference between the bone densities of the control and heparin groups (p<0·05), with the heparin group having lower bone density. The incidence of curves between the heparin and control groups were not statistically significant (p>0·01) (table). The magnitude of curves in scoliotic rats for the heparin group was 11·8° (SD 3·75) and for the control group 10° (4·3). The difference between the groups was not significant (p>0·05). Conclusions. This study involved rats with normal melatonin levels and both groups showed a high frequency of scoliosis incidence. Although no significant differences were recorded between groups, the results suggest that bipedality is a cause for scoliosis, and low bone mineral density may further increase this tendency

Aims

The aim of this study was to determine whether there is an increased prevalence of scoliosis in patients who have suffered from a haematopoietic malignancy in childhood.