Triptolide ameliorates osteoarthritis by regulating nuclear factor kappa B-mediated inflammatory response.

OBJECTIVES: Osteoarthritis (OA) is a joint degenerative disease that commonly occurs in older people and affect the quality of life. Triptolide (TPL), a compound derived from Tripterygium wilfordii, has been shown to exhibit anti-inflammatory properties. Here, we investigated the therapeutic effect of TPL on the experimental OA as well as the underlying molecular mechanisms. METHODS: OA models were established using monosodium iodoacetate (MIA) or surgery. The arthritis score and paw withdrawal threshold value of knees were used to evaluate the degree of arthritis. The level and expression of proinflammatory cytokines were evaluated by quantitative real-time PCR and ELISA kits. KEY FINDINGS: In surgery and MIA-induced OA rats, TPL alleviated arthritis symptoms and reduced inflammatory cytokine production in serum. In primary chondrocytes, TPL dose-dependently reversed lipopolysaccharide (LPS)-induced cell proliferation. Moreover, LPS-induced cell apoptosis and the expressions of proinflammatory cytokines interleukin-(IL-)6, IL-8, IL-1ß, IL-12, tumour necrosis factor-α (TNF-α) and interferon-gamma (INF-γ) were also attenuated by TPL. Mechanistically, the therapeutic effects of TPL on OA were effective by dampening nuclear factor kappa B (NF-κB) activity leading to reduced proinflammatory cytokines production and inflammatory response. CONCLUSIONS: TPL acts as an effective therapeutic drug for OA by mediating NF-κB signalling, thereby leading to the reduced proinflammatory cytokines production and inflammatory response.

PPAR-γ agonist pioglitazone alleviates inflammatory response induced by lipopolysaccharides in osteoblast cells.

Osteomyelitis is an acute or chronic inflammatory bone disease with a high disability rate. As an anti-inflammatory factor, peroxisome proliferator activated receptor-γ (PPAR-γ) is not only implicated in a variety of inflammatory responses but also regulates osteoblast differentiation and bone mass. However, the role of PPAR-γ in osteomyelitis is not fully understood. In the present study, we demonstrated that PPAR-γ showed a lower expression level in infected bone tissue of osteomyelitis patients as compared with uninfected bone tissue from nonosteomyelitis patients with fracture of the hip. We applied lipopolysaccharides (LPSs) in MC3T3-E1 osteoblast precursor cell line as an in vitro model for osteomyelitis. LPS treatment increased osteomyelitis-associated inflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), whereas PPAR-γ levels and cell viability in MC3T3-E1 cells were suppressed. PPAR-γ antagonist GW9662 further enhanced IL-6 and TNF-α levels, and decreased cell viability in the presence of LPS treatment. In contrast, PPAR-γ agonist pioglitazone antagonized the effect of LPS treatment in MC3T3-E1 cells. These findings suggest that PPAR-γ downregulation is associated with the inflammation and progression of osteomyelitis, and PPAR-γ agonist could serve as a therapeutic strategy to attenuate inflammatory responses. This study provides novel insights into the physiopathogenesis of osteomyelitis and future study is required to validate the findings in animal model and uncover the molecular mechanism of PPAR-γ-dependent anti-inflammation in osteoblasts.

Circular RNA circPDSS1 promotes osteosarcoma progression by sponging miR-502-3p and miR-4436a.

Osteosarcoma (OS) is a highly aggressive bone cancer. Patients with OS frequently develop drug resistance in clinical treatment, and the prognosis has not been improved significantly. There is an urgent need to identify novel markers and therapeutic targets. In this study, we focused on the highly expressed noncoding circular RNA circPDSS1 in OS, and studied its functional roles and downstream targets in OS cells by CCK-8, clone formation assay, transwell assays. Additionally, we performed luciferase reporter assay, RNA pull-down experiment and qRT-PCR to validate the micoRNA targets of circPDSS1. The involvement of circPDSS1 in tumorigenesis was also investigated in mouse xenografts model. The expression of circPDSS1 was significantly upregulated in OS tissues and cell lines. Patients with high circPDSS1 expression were associated with poorer progression-free survival (PFS) and overall survival (OS) as compared to those with low circPDSS1 expression. CircPDSS1 knockdown significantly inhibited the viability, clone formation ability and invasion ability of OS cells, and induced cell apoptosis, which were associated with the upregulation of proapoptotic proteins and the impairment of prosurvival signaling. Molecular mechanism study further demonstrated that circPDSS1 modulates OS cell functions by regulating the expression of miR-502-3p and miR-4436a. Our data suggest that circPDSS1 acts as a molecular sponge of miR-502-3p and miR-4436a regulates the proliferation and invasion of OS cells and promote the malignant progression of OS.

Osteoblast Response to Copper-Doped Microporous Coatings on Titanium for Improved Bone Integration.

Due to their excellent mechanical properties and good biocompatibility, titanium alloys have become a popular research topic in the field of medical metal implants. However, the surface of the titanium alloy does not exhibit biological activity, which may cause poor integration between the interface of the titanium implant and the interface of the bone tissue and subsequently may cause the implant to fall off. Therefore, surface biological inertness is one of the problems that titanium alloys must overcome to become an ideal orthopedic implant material. Surface modification can improve the biological properties of titanium, thereby enhancing its osseointegration effect. Copper is an essential trace element for the human body, can promote bone formation and plays an important role in maintaining the physiological structure and function of bone and bone growth and development. In this study, a microporous copper-titanium dioxide coating was prepared on the surface of titanium by microarc oxidation. Based on the evaluation of its surface characteristics, the adhesion, proliferation and differentiation of MC3T3-E1 cells were observed. A titanium rod was implanted into the rabbit femoral condyle, and the integration of the coating and bone tissue was evaluated. Our research results show that the microporous copper-titanium dioxide coating has a nearly three-dimensional porous structure, and copper is incorporated into the coating without changing the structure of the coating. In vitro experiments found that the coating can promote the adhesion, proliferation and differentiation of MC3T3-E1 cells. In vivo experiments further confirmed that the titanium copper-titanium dioxide microporous coating can promote the osseointegration of titanium implants. In conclusion, copper-titanium dioxide microporous coatings can be prepared by microarc oxidation, which can improve the biological activity and biocompatibility of titanium, promote new bone formation and demonstrate good osteoinductive properties. Therefore, the use of this coating in orthopedics has potential clinical application.

Comparison of unilateral and bilateral puncture percutaneous kyphoplasty in the treatment of osteoporotic vertebral compression fractures.

OBJECTIVES: To compare the clinical efficacy of unilateral and bilateral puncture PKP in the treatment of OVCFs and explored whether there is a difference in the efficacy of unilateral and bilateral puncture PKP after surgery. METHODS: A total of 98 patients with OVCFs treated by PKP from August 2016 to June 2018 were selected. There were 62 cases in the unilateral puncture group and 36 cases in the bilateral puncture group. The operation time, the amount of bone cement injection, the height of the anterior edge of the vertebral body and the visual analog scale (Visual Analog Scale, VAS) scores before and after the operation were analyzed, and whether the differences between the 2 groups were statistically significant was analyzed. RESULTS: All patients were followed up completely. The operation time and the number of X-ray fluoroscopies of the unilateral puncture group were significantly reduced compared to those of the bilateral group, and the difference was statistically significant (p<0.05). In terms of the bone cement injection volume, the average injection volume of the bilateral group was greater than that of the unilateral group, and the difference was statistically significant (p<0.05); the postoperative VAS scores of the 2 groups of patients were significantly improved, and the difference was statistically significant compared with that before surgery (p<0.05) but that of the unilateral group was not statistically significant compared with that of the bilateral group (p>0.05). The height of the anterior edge of the vertebral body in both groups was significantly improved compared with that before the operation, and the difference was statistically significant (p<0.05). CONCLUSION: Unilateral and bilateral puncture PKP can achieve good clinical efficacy in the treatment of osteoporotic vertebral compression fractures, but unilateral PKP has the advantages of short operation time and low X-ray exposure.

Increased expression of FOXD1 is associated with cervical node metastasis and unfavorable prognosis in oral squamous cell carcinoma.

BACKGROUND: Previous studies suggest that FOXD1 is involved in tumorigenesis and closely related to the patients' poor outcome in human cancer. However, its expression pattern in primary oral squamous cell carcinoma (OSCC) remains uncovered. In this study, we tried to explore the expression pattern of FOXD1 and its clinicopathological significance in primary OSCC. METHODS: Data mining and analysis on FOXD1 mRNA expression in OSCC samples were performed using publicly available databases. Its protein expression was supervised by immunohistochemistry in a retrospective cohort containing 58 primary OSCC samples. Furthermore, the potential associations between FOXD1 expression and various clinicopathological characteristics and patients' survival were further investigated. RESULTS: Bioinformatic analysis indicated that FOXD1 mRNA abundance was obviously up-regulated in OSCC cohorts. Immunohistochemical staining results showed that FOXD1 protein was significantly up-regulated in OSCC specimens as compared to normal counterparts and its aberrant up-regulation was remarkably related to cervical lymph node metastasis (P = .0198) and decreased overall survival (P = .0281) and disease-free survival (P = .0312). Both univariate and multivariate Cox regression analysis further revealed the expression pattern of FOXD1 as an independent prognostic factor for overall survival of patients. CONCLUSION: Taken together, these findings indicate that the aberrant up-regulation of FOXD1 is related to cervical node metastasis and unfavorable prognosis in OSCC and it also may play a key role during OSCC tumorigenesis and regard as a novel diagnostic and prognostic biomarker for OSCC.

Low dose of indomethacin and Hedgehog signaling inhibitor administration synergistically attenuates cartilage damage in osteoarthritis by controlling chondrocytes pyroptosis.

Blockade of Hedgehog signaling can prevent osteoarthritis (OA) syndromes. However, the amelioration of related inflammation condition is limited. The purpose of this study was to observe the effect of combined use of Hedgehog signaling inhibitor GANT-61 and common clinical anti-inflammatory drug indomethacin on cartilage injury and inflammation in experimental OA mice. We found that GANT-61 and indomethacin synergistically attenuate cartilage damage and serum levels of inflammatory cytokines TNF-α, IL-2 and IL-6 in OA mice. Moreover, in vitro treatment of GANT-61 and indomethacin synergistically reduced the mRNA expression of TNF-α, IL-2 and IL-6 in lipopolysaccharide (LPS)-stimulated C28/I2 chondrocytes. Mechasnistic studies showed that GANT-61 and indomethacin synergistically attenuate the expressions of cell pyroptosis-related genes caspase-1, IL-1ß and IL-18 at mRNA and protein level. To conclude, our study showed that GANT-61 and indomethacin had a synergistically ameliorating effect on osteoarthritis by mediating chondrocytes pyroptosis.