MINK1 deficiency stimulates nucleus pulposus cell pyroptosis and exacerbates intervertebral disc degeneration.

Intervertebral disc (IVD) degeneration, induced by aging and irregular mechanical strain, is highly prevalent in the elderly population, serving as a leading cause of chronic low back pain and disability. Evolving evidence has revealed the involvement of nucleus pulposus (NP) pyroptosis in the pathogenesis of IVD degeneration, while the precise regulatory mechanisms of NP pyroptosis remain obscure. Misshapen/Nck-interacting kinase (NIK)-related kinase 1 (MINK1), a serine-threonine protein kinase, has the potential to modulate the activation of NLRP3 inflammasome, indicating its pivotal role in governing pyroptosis. In this study, to assess the significance of MINK1 in NP pyroptosis and IVD degeneration, NP tissues from patients with varying degrees of IVD degeneration, and IVD tissues from both aging-induced and lumbar spine instability (LSI) surgery-induced IVD degeneration mouse models, with or without MINK1 ablation, were meticulously evaluated. Our findings indicated a notable decline in MINK1 expression in NP tissues of patients with IVD degeneration and both mouse models as degeneration progresses, accompanied by heightened matrix degradation and increased NP pyroptosis. Moreover, MINK1 ablation led to substantial activation of NP pyroptosis in both mouse models, and accelerating ECM degradation and intensifying the degeneration phenotype in mechanically stress-induced mice. Mechanistically, MINK1 deficiency triggered NF-κB signaling in NP tissues. Overall, our data illustrate an inverse correlation between MINK1 expression and severity of IVD degeneration, and the absence of MINK1 stimulates NP pyroptosis, exacerbating IVD degeneration by activating NF-κB signaling, highlighting a potential innovative therapeutic target in treating IVD degeneration.

Qiangguyin inhibited fat accumulation in OVX mice through the p38 MAPK signaling pathway to achieve anti-osteoporosis effects.

Postmenopausal osteoporosis (PMOP) is a common bone disease characterized by decreased bone density and increased bone fragility due to decreased estrogen levels. Qiangguyin (QGY) is transformed from the famous traditional Chinese medicine BuShen Invigorating Blood Decoction. In this study, we used QGY to treat PMOP. We observed that QGY significantly reduced fat accumulation in the chondro-osseous junction. However, its specific mechanism of action remains unclear. To determine the specific molecular mechanism of QGY, we explored the pharmacological mechanism by which QGY reduces fat accumulation in the chondro-osseous junction through network pharmacological analysis. The active components and targets related to PMOP and QGY were screened from different databases, forming a composition-target-disease network. Next, a comprehensive analysis platform including protein-protein interaction (PPI) network, Gene Ontology (GO) enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were established. The results revealed that QGY inhibits adipogenic differentiation by activating the mitogen-activated protein kinase (MAPK) signaling pathway, thus reducing the accumulation of fat in the chondro-osseous junction. For further verification. In vitro and in vivo experiments were carried out. Our data showed that QGY significantly reversed the high expression of fatty acid binding protein 4 (FABP4) and peroxisome proliferator-activated receptor γ (PPARγ). Further, QGY prevents fat accumulation by inhibiting the expression of p38. In summary, the results of this study suggested that QGY-induced phenotypic changes are related to the activation of the p38 MAPK signaling pathway.

Efficacy and Safety of Posterior Long-Segment Fixation Versus Posterior Short-Segment Fixation for Kummell Disease: A Meta-Analysis.

Purpose: Posterior short-segment fixation (SSF) and long-segment fixation (LSF) are two methods for the treatment of Kummell disease, but the safety and effectiveness of these two surgical methods still lack adequate medical evidence. This study aimed to evaluate the two methods. Methods: Database searches for randomized controlled trials, case-control studies, and cohort studies of posterior SSF and posterior LSF in the treatment of Kummell disease were performed. After the document quality was evaluated with the Newcastle-Ottawa Quality Assessment Scale, a meta-analysis was carried out. Results: Meta-analysis revealed that the operation time and intraoperative blood loss in the LSF group were higher than those in the SSF group [MD = -18.17, 95% CI (-30.31, -6.03), z = 2.93, P = .003; MD = -82.07, 95% CI (-106.91, -57.24], z = 6.48, P < .00001). The postoperative last follow-up local kyphosis angle in the SSF group was greater than that in the LSF group (MD = 3.18, 95% CI [.56, 5.81], z = 2.38, P = .02), and there were no significant differences in perioperative complications, bone cement leakage rate, incidence of adverse events during follow-up, postoperative follow-up visual analog scale, postoperative Oswestry dysfunction index, and postoperative immediate local kyphosis angle between the two groups (P > .05). Conclusion: SSF and LSF are effective and safe for the treatment of Kummell disease. SSF can reduce the operation time and intraoperative bleeding; LSF can better maintain the long-term stability of kyphosis. The methods should be evaluated by clinicians according to the individual situation of the patients.

Percutaneous Vertebroplasty Combined with Zoledronic Acid in Treatment and Prevention of Osteoporotic Vertebral Compression Fractures: A Systematic Review and Meta-Analysis of Comparative Studies.

OBJECTIVE: This study was designed to help elucidate the benefits and advantages of vertebroplasty combined with zoledronic acid (ZOL) versus vertebroplasty alone, to provide clinical recommendations for the treatment of osteoporotic vertebral compression fractures (OVCFs) considering the current best-available evidence. METHODS: We comprehensively searched PubMed, Embase, Web of Science, and the Cochrane Library and performed a systematic review and cumulative meta-analysis of all randomized controlled trials and retrospective comparative studies assessing these important indexes of 2 methods using Review Manager 5.4. RESULTS: Four randomized controlled trials and 4 retrospective studies including 2335 cases were identified. Vertebroplasty combined with ZOL was associated with benefits from decreased pain (weighted mean difference [WMD] -0.43; 95% confidence interval [CI] -0.59 to -0.27; P < 0.05), increased function (WMD -4.94; 95% CI -6.13 to -3.75; P < 0.05), increased BMD of the vertebral body(WMD 0.85; 95% CI 0.30-1.40; P < 0.05) and of the proximal femoral neck (WMD 0.14; 95% CI 0.08-0.21; P < 0.05), fewer markers of bone metabolism (N-terminal molecular fragment: WMD -4.82; 95% CI -6.08 to -3.55; P < 0.05; procollagen type I N-terminal propeptide: WMD -17.31; 95% CI -18.04 to -16.58; P < 0.05; beta collagen degradation product: WMD -0.27; 95% CI -0.35 to -0.19; P < 0.05), and lower rate of refracture (1.54% and 12.6%; odds ratio 0.17; 95% CI 0.08-0.36; P < 0.05). Patients in the vertebroplasty combined with ZOL group had greater vertebral body height (WMD 2.17; 95% CI 0.72-3.62; P < 0.05) than in the vertebroplasty group, but no differences on Cobb angle were observed (WMD -1.18; 95% CI -2.47 to 0.10; P > 0.05). CONCLUSIONS: Vertebroplasty combined with ZOL was superior to vertebroplasty alone in terms of BMD, bone metabolism makers, refracture rate, pain and function.

USF2 reduces BMP3 expression via transcriptional activation of miR-34a, thus promoting osteogenic differentiation of BMSCs.

INTRODUCTION: Osteoporosis is the most susceptible disease for people over 60. The main cause of osteoporosis is the decreased osteogenic differentiation of mesenchymal stem cells (MSCs). Here we showed that upstream stimulatory factor 2 (USF2)/microRNA-34a (miR-34a)/bone morphogenetic protein 3 (BMP3) axis regulated osteogenic differentiation of BMSCs. MATERIALS AND METHODS: USF2 and miR-34a expression were examined using qPCR. Protein levels of BMP3 and osteogenic markers expression were evaluated using both western blot and qPCR. Activity of ALP was determined by ALP assay kit. Mineralization capacity of hBMSCs was assessed using ARS. Besides, CHIP assay was employed to verify whether USF2 could bind to miR-34a promoter. Finally, RIP assay and dual-luciferase reporter assay were employed to verify whether miR-34a directly bound to BMP3. RESULTS: Our results suggested that miR-34a was upregulated during osteogenic differentiation of BMSCs, and miR-34a overexpression could enhance osteogenic differentiation of BMSCs. USF2 could positively regulate miR-34a expression by interacting with its promoter. USF2 overexpression enhanced osteogenic differentiation of BMSCs, while miR-34a inhibition reversed the effect. Besides, BMP3 was the target of miR-34a. MiR-34a overexpression enhanced osteogenic differentiation of BMSCs, which was abolished by BMP3 overexpression. CONCLUSION: Taken together, USF2 enhanced osteogenic differentiation of BMSCs via downregulating BMP3 by interacting with miR-34a promoter.

Artesunate promotes osteoblast differentiation through miR-34a/DKK1 axis.

BACKGROUND: Osteoporosis is characterised by impairment of microarchitecture and bone mass. Therapeutic strategy promoting osteoblast differentiation is considered as a promising direction for the treatment of osteoporosis. Artesunate (ART) is related to osteoporosis, but the relationship between ART and osteogenic differentiation is still unknown. METHODS: Cells proliferation were measured by MTT, ALP activity assay and Alizarin Red S staining were used to assess osteogenic differentiation of hBMSCs. Western blotting and qRT-PCR were applied for measuring expression of protein and mRNA, respectively. The relationship between miR-34a and Dickkopf-1 (DKK1) was detected by dual luciferase reporter assay. RESULTS: The expression of osteoblasts differentiation related proteins (Runx2, OCN, and OPN) were significantly increased by ART. And ART accelerates the osteoblasts differentiation of hBMSCs through promoting Wnt signaling pathway by DKK1 inhibition. Significant higher expression of miR-34a and lower expression of DKK1 could be induced by ART. We firstly proved that miR-34a could bind DKK1 specifically. CONCLUSION: ART could promote osteoblast differentiation through miR-34a/DKK1/Wnt pathway. Therefore, our findings may provide a new thought for the treatment of osteoporosis by ART through osteoblast differentiation promotion.

Complete L5 burst fracture treated by 270-degree decompression and reconstruction using titanium mesh cage via a single posterior vertebrectomy.

Complete burst fractures of the L5 is relatively uncommon. How to accomplish a rigid internal fixation as well as preserve motor function is an enormous challenge. We report such a case treated via a single posterior vertebrectomy with 270-degree decompression and reconstruction using titanium mesh cage. The disc between L5/S1 was preserved by placing the titanium mesh cage on the inferior endplate of the L5. We hope this method can offer a possible solution for other surgeons when they meet a similar fracture pattern.

[Clinical applications of sternoclavicular hook plate for the treatment of sternoclavicular joint dislocation].

OBJECTIVE: To observe the clinical therapeutic effects of sternoclavicular hook plate for the treatment of sternoclavicular joint dislocation. METHODS: From June 2010 to June 2012, 7 patients with sternoclavicular joint dislocation were treated with sternoclavicular hook plate fixation. Among the 7 patients, 5 patients were male and 2 patients were female, and the average age was 42.3 years, ranging from 38 to 54 years. The course of the disease ranged from 1 to 4 weeks. All the patients had trauma history. The clinical manifestations included: obvious swelling and pain of sternoclavicular joint, restricted shoulder joint activity. The sternoclavicular joint dislocation was proved by preoperative X-ray and CT. The postoperative curative effect was evaluated according to Rockwood scoring method. RESULTS: According to Rockwood scoring method, the excellent results obtained in 6 cases, good in 1. There were no complications such as internal fixation loosening or broken, second dislocation, pain in the sternoclavicular joint, and deformity. The function of shoulder joint was good, and the limb activity was free and no pain appeared. CONCLUSION: The sternoclavicular hook plate for the treatment of sternoclavicular joint dislocation has follow advantages: simple procedure, stable fixation, definite therapeutic effects.

[A short-term follow-up results of lumbar disc herniation by Coflex].

OBJECTIVE: To evaluate the short term effectiveness of lumbar disc herniation by Coflex. METHODS: From December 2007 to June 2008, 31 patients (16 males and 15 females) were treated by Coflex. The average age was 51.4 years (range, 33 - 70 years). The average period of follow-up was 10 months. To evaluate the short term effectiveness of lumbar disc herniation by Coflex by JOA, VAS, the conventional radiography and oswestry disability index (ODI). RESULTS: The average JOA score increased from 9.1 +/- 1.1 preoperatively to 26.4 +/- 1.7 at 6 month postoperatively. ODI decreased from 24.7 +/- 4.8 preoperatively to averaged 4.5 +/- 1.1 at 6 months postoperatively. The VAS score decreased from 7.9 +/- 0.8 to 3.0 +/- 0.9. The clinical symptoms after operation were improved significantly. There were statistically significant differences between the preoperative and postoperative HD (height of dorso- intervertebral discs), DS(distance across the two adjacent spinous processes), DI (distance of intervertebral foramina). The average HD increased from (7.9 +/- 1.1) mm preoperatively to (10.8 +/- 1.3) mm after operation. The average DS increased from (28.3 +/- 2.4) mm preoperatively to (36.4 +/- 1.7) mm postoperatively. The average DI changed from (18.8 +/- 1.0) mm preoperatively to (21.6 +/- 1.7) mm postoperatively. Complications occurred in 3 patients (9.6%). One case complained of persistent low back pain. One case showed opposite lower limb pain in 3 weeks after operation, and was cured after appropriate treatment. One case had the loosening of Coflex in 6 months after surgery, but did not appear related clinical symptoms. CONCLUSION: Coflex for lumbar disc herniation can increase the HD and DI significantly, and it has positive meaning for keeping height of lumbar vertebral space and treating the nerve root symptom of lumbar disc herniation.