Exogenous iron caused osteocyte apoptosis, increased RANKL production, and stimulated bone resorption through oxidative stress in a murine model.

Iron overload is a risk factor for osteoporosis due to its oxidative toxicity. Previous studies have demonstrated that an excessive amount of iron increases osteocyte apoptosis and receptor activator of nuclear factor κ-B ligand (RANKL) production, which stimulates osteoclast differentiation in vitro. However, the effects of exogenous iron supplementation-induced iron overload on osteocytes in vivo and its role in iron overload-induced bone loss are unknown. This work aimed to develop an iron overloaded murine model of C57BL/6 mice by intraperitoneal administration of iron dextran for two months. The iron levels in various organs, bone, and serum, as well as the microstructure and strength of bone, apoptosis of osteocytes, oxidative stress in bone tissue, and bone formation and resorption, were assessed. The results showed that 2 months of exogenous iron supplementation significantly increased iron levels in the liver, spleen, kidney, bone tissue, and serum. Iron overload negatively affected bone microstructure and strength. Osteocyte apoptosis and empty lacunae rate were elevated by exogenous iron. Iron overload upregulated RANKL expression but had no significant impact on osteoprotegerin (OPG) and sclerostin levels. Static and dynamic histologic analyses and serum biochemical assay showed that iron overload increased bone resorption without significantly affecting bone formation. Exogenous iron promoted oxidative stress in osteocytes in vivo and in vitro. Additional supplementation of iron chelator (deferoxamine) or N-acetyl-L-cysteine (NAC) partially alleviated bone loss, osteocyte apoptosis, osteoclast formation, and oxidative stress due to iron overload. These findings, in line with prior in vitro studies, suggest that exogenous iron supplementation induces osteoclastogenesis and osteoporosis by promoting osteocyte apoptosis and RANKL production via oxidative stress.

CKM and TERT dual promoters drive CRISPR-dCas9 to specifically inhibit the malignant behavior of osteosarcoma cells.

Improvements in treatment and chemotherapy have increased the survival rate of osteosarcoma, but overall efficacy remains low, highlighting the need for new gene therapy methods. Clustered regularly interspaced short palindromic repeats-deactivated Cas9 (CRISPR-dCas9) technology offers a promising strategy, but targeting osteosarcoma cells precisely is a challenge. We designed a system to achieve specific expression of CRISPR-dCas9-KRAB in osteosarcoma cells by using the creatine kinase muscle (CKM) promoter to drive dCas9-KRAB and the telomerase reverse transcriptase (TERT) promoter to drive single guide (sg)RNA expression. We inhibited the MDM2 proto-oncogene using this system in vitro, which efficiently inhibited the malignant behavior of osteosarcoma cells and induced apoptosis without affecting normal cells. In vivo experiments demonstrated that this system effectively inhibited the growth of subcutaneously transplanted tumors in nude mice. These findings provide a new method for precise identification and intervention of osteosarcoma with significant implications for the development of gene therapy methods for other cancers. Future research should focus on optimizing this system for clinical translation.

Iron Oxide Nanoparticles Combined with Static Magnetic Fields in Bone Remodeling.

Iron oxide nanoparticles (IONPs) are extensively used in bone-related studies as biomaterials due to their unique magnetic properties and good biocompatibility. Through endocytosis, IONPs enter the cell where they promote osteogenic differentiation and inhibit osteoclastogenesis. Static magnetic fields (SMFs) were also found to enhance osteoblast differentiation and hinder osteoclastic differentiation. Once IONPs are exposed to an SMF, they become rapidly magnetized. IONPs and SMFs work together to synergistically enhance the effectiveness of their individual effects on the differentiation and function of osteoblasts and osteoclasts. This article reviewed the individual and combined effects of different types of IONPs and different intensities of SMFs on bone remodeling. We also discussed the mechanism underlying the synergistic effects of IONPs and SMFs on bone remodeling.

[Clinical efficacy of endoscopy in the treatment of lumbar disc herniation combined with posterior apophyseal ring separation].

OBJECTIVE: To investigate the efficacy and safety of total spine endoscopy in the treatment of lumbar disc herniation combined with posterior apophyseal ring separation. METHODS: From January 2015 to January 2018, a total of 21 patients with lumbar disc herniation complicated with posterior apophyseal ring separation were treated with total spine endoscopy via interlamina approach. There were 17 males and 4 females. The age ranged from 18 to 48 years old and the median age was 27 years old. All were single segment unilateral disc herniation, interlaminar approach was adopted, and the herniated disc was removed unilaterally at the symptomatic side under the microscope, and all or part of the broken bonewas removed. RESULTS: There were no complications such as incision infection, intervertebral space infection, intestinal injury, dural injury and cerebrospinal fluid leakage. The operation time ranged from 32 to 92 minutes and the median time was 57 minutes. Postoperative imaging examination showed that 2 patients had complete resection of osteotomy of posterior edge of vertebral body, 16 patients had partially resection and 3 patients had no resection. All intervertebral discs were completely removed. All 21 patients were followed up, and the duration ranged from 12 to 36 months, with a median of 15 months. The VAS of lumbago was 7.10±1.20 before surgery, 3.46±0.23 on the 3rd day after surgery, 2.36±0.19 on the 6th month after surgery; and the VAS of leg pain was 8.80±0.55 before surgery, 3.54±0.28 on the 3rd day after surgery, and 2.59±0.26 on the 6th month after surgery. The Oswestry Disability Index score was (69.71±9.37)% before surgery, (32.19±6.95)% on the 6th month after surgery, and (20.95± 6.16)% at the latest follow up. Onthe 1st year after operation, 16 patients got an excellent result, 4 good and 1 fair according to Macnab evaluation system. CONCLUSION: Total spine endoscopy via interlaminal approach can be used as an option in the treatment of lumbar disc herniation combined with vertebral posterior margin dissociation, which can reduce trauma and injury to the lumbar dorsal muscle and achieve similar decompression effect as open surgery. The long term efficacy needs to be further proved by prospective randomized controlled studies with larger sample size.