Osteoporosis (OP) is a systemic bone metabolic disease that results from an imbalance between bone formation and bone resorption. The accumulation of iron has been identified as an independent risk factor for osteoporosis. Ferroptosis, a novel form of programmed cell death, is driven by iron-dependent lipid peroxidation. Nevertheless, the precise role of ferroptosis in iron accumulation-induced osteoporosis remains uncertain. We utilized proteomics and ELISA to screen key regulatory molecules related to iron accumulation in osteoporosis populations. HE staining was used to assess osteocyte changes in Hamp knockout (KO) iron accumulation mouse models. Western Blot, qPCR, ALP staining, and Alizarin Red staining were employed to explore the effects of siRNA-mediated gene knockdown on osteogenic differentiation in the MC3T3 cell line. ELISA, micro-CT, von Kossa staining, toluidine blue staining, TRAP staining, and calcein analysis were used to study the bone phenotype of conditional gene knockout mice. RNA-seq, endoplasmic reticulum activity probes, transmission electron microscopy (TEM), Western Blot, co-immunoprecipitation (Co-IP), flow cytometry, and ChIP-seq were employed to investigate the regulatory mechanisms of the target gene in osteogenic differentiation. OVX and Hamp KO mice were used to establish osteoporosis models, and AAV-mediated overexpression was employed to explore the intervention effects of the target gene on osteoporosis. The experiments demonstrate that iron accumulation can lead to changes in COPB1 expression levels in bone tissue. Cellular and animal experiments revealed that COPB1 deficiency reduces the osteogenic ability of osteoblasts. Transcriptome analysis and phenotypic experiments revealed that COPB1 deficiency induces ferroptosis and endoplasmic reticulum stress in cells. Further investigation confirmed that COPB1 plays a key role in endoplasmic reticulum stress by inhibits SLC7A11 transcription via ATF6. This reduces cystine uptake, ultimately inducing ferroptosis. Overexpression of COPB1 can restore osteogenic function in both cells and mice. This study elucidated the essential role of COPB1 in maintaining bone homeostasis and highlights it as a potential therapeutic target for treating iron accumulation-related osteoporosis. Our data elucidate the critical role of COPB1 in maintaining bone homeostasis and demonstrate that COPB1 can directly promote bone formation, making it a potential therapeutic target for the future treatment of osteoporosis.

Background Cervical spondylotic myelopathy (CSM) caused by multi-segment cervical stenosis is a common spinal surgery disease with severe neurological dysfunction. The surgical goal was to achieve full canal decompression while minimizing damage to the normal structures. Unilateral biportal endoscopy (UBE), due to its good visualization, independent view-working portals, and wider instrument availability, can be utilized to efficiently and safely complete a laminectomy under endoscopy. Objective This study was to determine the efficiency and safety of a novel cervical laminectomy technique and introduce some new endoscopic anatomic concepts. Methods We report on 3 cases of multi-segment of cervical stenosis. The author attempted combinations of "laminectomy", "hemilaminectomy", and "ligamentum flavum resection" under UBE for different cervical cases. The postoperative neurological improvement and perioperative complications were used to determine the efficiency and safety. Results All 3 patients got significant improvement after surgery. And no complication was observed. This study described in detail the surgical steps and introduced new anatomic concepts that "infraspinous absence range (IS-AR)" and "ligamentum flavum-interspinous space (LF-IS space)". Conclusion Central laminectomy for bilateral decompression (CLBD) under UBE is an effective surgical method for the treatment of CSM caused by multi-segment cervical spinal stenosis. It can achieve the same decompression effect as traditional open cervical laminectomy while protecting the paraspinal muscles and posterior ligament complex which can avoid postoperative axial symptoms and cervical stiffness. However, due to the small size of the spinal canal and the small perturbation tolerance of the cervical spinal cord, the learning curve will be slightly high. China Clinical Trial registration number：ChiCTR2200065144.