No abstract

Interleukin (IL)-6 is known to indirectly enhance osteoclast formation by promoting receptor activator of nuclear factor kappa-B ligand (RANKL) production by osteoblastic/stromal cells. However, little is known about the direct effect of IL-6 on osteoclastogenesis. Here, we determined the direct effects of IL-6 and its soluble receptor (sIL-6R) on RANKL-induced osteoclast formation by osteoclast precursors in vitro. We found IL-6/sIL-6R significantly promoted and suppressed osteoclast differentiation induced by low- (10 ng/ml) and high-level (50 ng/ml) RANKL, respectively. Using a bone resorption pit formation assay, expression of osteoclastic marker genes and transcription factors confirmed differential regulation of RANKL-induced osteoclastogenesis by IL-6/sIL-6R. Intracellular signaling transduction analysis revealed IL-6/sIL-6R specifically upregulated and downregulated the phosphorylation of NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells), ERK (extracellular signal–regulated kinase) and JNK (c-Jun N-terminal kinase) induced by low- and high level RANKL, respectively. Taken together, our findings demonstrate that IL-6/sIL-6R differentially regulate RANKL-induced osteoclast differentiation and activity through modulation of NF-κB, ERK and JNK signaling pathways. Thus, IL-6 likely plays a dual role in osteoclastogenesis either as a pro-resorption factor or as a protector of bone, depending on the level of RANKL within the local microenvironment.

COVID-19 mRNA vaccines contain synthetic mRNA sequences encoded for the Spike proteins expressed on the surface of SARS-CoV-2, and utilize the host cells to produce specific antigens that stimulate both humoral and cellular immunities. Lipid nanoparticles are essential to facilitate the intracellular delivery of the mRNA to its action site, the ribosome, to fully exert its effect.

Object During the past decades, lumbar fusion has increasingly become a standard treatment for degenerative spinal disorders. However, it has also been associated with an increased incidence of adjacent-segment degeneration (ASD). Previous studies have reported less ASD in anterior fusion surgeries; thus, the authors hypothesized that the integrity of the posterior complex plays an important role in ASD. This study was designed to investigate the effect of the posterior complex on adjacent instability after lumbar instrumentation and the development of ASD. Methods To evaluate different surgical interventions, 120 patients were randomly allocated into 3 groups of 40 patients each who were statistically similar with respect to demographic and clinical data. Patients in Group A were allocated for facet joint resection and L4–5 fusion, Group B for semilaminectomy and fusion, and Group C for complete laminectomy and fusion. All of the patients were followed up for 5–7 years (mean 5.9 years). The disc height, intervertebral disc angle, dynamic intervertebral angular range of motion (ROM), L3–4 slip, and the total lordosis angle were each measured before the operation and at the final follow-up. The Japanese Orthopaedic Association (JOA) score was determined before surgery and at the final follow-up to evaluate the clinical results. Results Among the 3 groups, no significant differences were detected in all clinical and demographic assessments before surgery. At 3 months after surgery, the JOA score of all groups improved significantly and showed no significant differences among the groups. At the final follow-up, Group C had a significantly (p < 0.05) lower JOA score than the other 2 groups. Moreover, the disc height and total lumbar lordosis in patients of Group C were significantly decreased compared with disc height and total lumbar lordosis in the other 2 groups. In contrast, disc angle, dynamic angular ROM, and listhesis were significantly higher in Group C than in the other 2 groups. Twenty-four patients showed signs of ASD after the operation (3 patients in Group A, 4 in B, and 17 in C). The number of patients in Group C showing ASD was significantly different from that in Groups A and B. Conclusions During follow-up for 6 years, a significantly higher number of patients with ASD were noted in the complete-laminectomy group. The number of reoperations for treating ASD was much higher in this patient group than in the patients undergoing facet joint resection and L4–5 fusion or semilaminectomy and fusion. Therefore, preserving the posterior complex as much as possible during surgery plays an important role in preventing ASD and in reducing the reoperation rate.

Chitosan oligosaccharide (COS), a partially hydrolysed product of chitosan, has various important biological activities.