Circular RNA circ_0020014 contributes to osteoarthritis progression via miR-613/ADAMTS5 axis.

Circular RNAs (circRNAs) have been shown to be significant regulators in osteoarthritis (OA), whereas the functional effect of circ_0020014 in OA remains unclear. Our goal was to try and understand the underlying regulatory mechanism of circ_0020014 in OA. The cartilage tissue was obtained from OA patients and trauma patients. Interleukin-1ß (IL-1ß)-treated chondrocytes (CHON-001) were used as the in vitro cellular model for OA. The expression levels of circ_0020014, microRNA-613 (miR-613), and a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5) were examined by real-time quantitative polymerase chain reaction (RT-qPCR). The protein level was detected using the western blot assay. Cell viability and apoptosis were measured by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-2H-tetrazol-3-ium bromide (MTT) and flow cytometry assays, respectively. The secretion of inflammatory cytokine was determined by enzyme-linked immunosorbent assay (ELISA). Circ_0020014 was upregulated in OA cartilage tissues and IL-1ß-treated CHON-001 cells, compared with that in healthy cartilage tissues and untreated cells. IL-1ß treatment induced cell injury by promoting inflammation and apoptosis, and inhibiting cell viability and extracellular matrix (ECM) accumulation in chondrocytes. Circ_0020014 knockdown significantly protected CHON-001 cells from IL-1ß-induced cell dysfunction. MiR-613 was targeted by circ_0020014 and negatively regulated ADAMTS5 expression. In addition, miR-613 downregulation or ADAMTS5 overexpression partly lessened the protective effect of circ_0020014 knockdown on IL-1ß-treated CHON-001 cells. Collectively, circ_0020014 acted as a miR-613 sponge to regulate ADAMTS5 expression, thereby protecting chondrocytes from IL-1ß-induced inflammatory damage, which might be a novel diagnostic marker for OA.

Circ_DHRS3 positively regulates GREM1 expression by competitively targeting miR-183-5p to modulate IL-1ß-administered chondrocyte proliferation, apoptosis and ECM degradation.

BACKGROUND: Osteoarthritis (OA) is a chronic inflammatory disease caused by degenerative changes of articular cartilage, involving in the expression changes of special circular RNAs (circRNAs). This study aimed to explore the role of circ_DHRS3 in OA cell models and provide a potential mechanism. METHODS: OA cell models were constructed using human chondrocytes with Interleukin-1 beta (IL-1ß) treatment. The expression of circ_DHRS3, microRNA (miR)-183-5p and Gremlin 1 (GREM1) mRNA was detected using real-time quantitative polymerase chain reaction (RT-qPCR). Cell proliferation was identified using 3-[4, 5-dimethylthiazol-2-yl]-2, 5 diphenyl tetrazolium bromide (MTT) assay. Cell apoptosis was investigated using flow cytometry assay. The protein levels of proliferation- and apoptosis-related proteins were quantified by western blot. The levels of extracellular matrix (ECM)-associated proteins were quantified by western blot to assess ECM degradation. The relationship between miR-183-5p and circ_DHRS3 or GREM1 was predicted and then verified by dual-luciferase reporter assay. RESULTS: Circ_DHRS3 expression was elevated in OA cartilage tissues and IL-1ß-treated chondrocytes. Circ_DHRS3 was resistant to RNase R and Actinomycin D. Circ_DHRS3 knockdown promoted chondrocyte proliferation inhibited by IL-1ß, and alleviated IL-1ß-induced apoptosis and ECM degradation, which were reversed by the inhibition of miR-183-5p, a target of circ_DHRS3. MiR-183-5p restoration also enhanced IL-1ß-blocked cell proliferation, and relieved IL-1ß-induced cell apoptosis and ECM degradation, while GREM1 (a target of miR-183-5p) overexpression abolished the effects of miR-183-5p restoration. Moreover, circ_DHRS3 regulated GREM1 expression by targeting miR-183-5p. CONCLUSION: Circ_DHRS3 mediated IL-1ß-administered chondrocyte proliferation, apoptosis and ECM degradation by positively regulating GREM1 expression via competitively targeting miR-183-5p.

Effects of teriparatide versus alendronate for treatment of postmenopausal osteoporosis: A meta-analysis of randomized controlled trials.

OBJECTIVES: Osteoporosis remains a clinical challenge. Teriparatide is an anabolic drug and alendronate is an antiresorptive agent; both are used in the treatment of osteoporosis. Comprehensive reviews investigating the comparative safety and efficacy of teriparatide versus alendronate are scarce. Therefore, we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the safety and efficacy of teriparatide versus alendronate for the treatment of postmenopausal osteoporosis. METHODS: We conducted a comprehensive literature review of the PubMed, EMBASE, Cochrane Controlled Trials Registry, and the China Academic Journal Network Publishing databases for relevant RCTs of teriparatide versus alendronate in postmenopausal osteoporosis patients. Outcome measures were percentage change in lumbar spine and femoral neck bone mineral density (BMD) and incidence of vertebral and nonvertebral fractures. Effect size was reported as weighted mean differences (WMDs) for continuous outcomes and odds ratios (OR) for dichotomous outcomes, with associated 95% confidence intervals (CIs). RESULTS: Six trials involving 618 patients were included. The meta-analysis demonstrated a significant increase in lumbar spine BMD (WMD: 3.46, 95% CI: 2.15-4.77, P < .00001), but not femoral neck BMD (WMD = 1.50, 95% CI: 0.04-2.95, P = .04), in postmenopausal osteoporosis patients treated with teriparatide compared with alendronate for 6 to 18 months. These beneficial effects were apparent in the lumbar spine at 12 months of treatment (WMD: 4.49, 95% CI: 2.57-6.40, P < .01). Teriparatide was not superior to alendronate in reducing fracture risk (OR: -0.03, 95% CI: -0.12 to 0.07; P = .52). CONCLUSION: Teriparatide may be superior to alendronate for increasing lumbar spine BMD in postmenopausal osteoporosis. The efficacy and safety of long-term teriparatide and alendronate treatment in postmenopausal osteoporosis should be further investigated in clinical trials.

A comparison between unilateral transverse process-pedicle and bilateral puncture techniques in percutaneous kyphoplasty.

STUDY DESIGN: A prospective comparative study. OBJECTIVE: To assess the clinical and radiological outcomes for the treatment of osteoporotic vertebral compression fractures using unilateral transverse process-pedicle and bilateral percutaneous kyphoplasty (PKP). SUMMARY OF BACKGROUND DATA: PKP is a widely used vertebral augmentation procedure for treating painful vertebral compression fractures. A percutaneous bilateral approach is typically used to access the vertebral body. Many previous studies have reported excellent clinical results with PKP. In contrast, numerous complications and problems have also been reported, such as puncture difficulty, cement leakage, and adjacent vertebral fracture. METHODS: This prospective study included 316 patients with single-level lumbar osteoporotic vertebral compression fracture, 224 females and 92 males with a mean age of 71.5 years. Randomized patients underwent PKP using 2 different puncture techniques. The patients were followed up postoperatively and were assessed mainly with regard to clinical and radiological outcomes. Clinical outcomes were evaluated mainly using the visual analogue scale for pain and 36-Item Short Form Health Survey (SF-36) questionnaire for health status. Radiological outcomes were assessed mainly on the basis of radiation dose, bone cement distribution, vertebral body height, and kyphotic angle. RESULTS: Patients were followed up from 12 to 28 months, with an average of 16.8 months. One hundred fifty-eight patients were treated with unilateral method and 151 patients were treated with bilateral method. In the unilateral group, the volume of the injected cement and radiation dose were significantly less than that in the bilateral group. All patients in both groups had significantly less pain after the procedures, compared with their preoperative period pain. No statistically significant differences were observed when visual analogue scale and 36-Item Short Form Health Survey were compared between the groups. Both unilateral and bilateral groups showed insignificant decrease in the kyphotic angle during the follow-ups. The kyphotic angle in the unilateral group improved more significantly than in the bilateral group. In the bilateral group, 16 patients had obvious pain in the puncture sites at 1 month postoperatively caused by facet joint violation. With local block treatment, the pain disappeared in all patients at the last follow-up. CONCLUSION: Both bilateral and unilateral PKP are relatively safe and provide effective treatment for patients with painful osteoporotic vertebral compression fracture. However, unilateral PKP received less radiation dose and operation time, it also offered a higher degree of deformity correction and resulted in less complication than bilateral PKP.

MALDI-TOF-MS serum protein profiling for developing diagnostic models and identifying serum markers for discogenic low back pain.

BACKGROUND: The identification of the cause of chronic low back pain (CLBP) represents a great challenge to orthopedists due to the controversy over the diagnosis of discogenic low back pain (DLBP) and the existence of a number of cases of CLBP of unknown origin. This study aimed to develop diagnostic models to distinguish DLBP from other forms of CLBP and to identify serum biomarkers for DLBP. METHODS: Serum samples were collected from patients with DLBP, chronic lumbar disc herniation (LDH), or CLBP of unknown origin, and healthy controls (N), and randomly divided into a training set (n = 30) and a blind test set (n = 30). Matrix-assisted laser desorption ionization time-of-flight mass spectrometry was performed for protein profiling of these samples. After the discriminative ability of two most significantly differential peaks from each two groups was assessed using scatter plots, classification models were developed using differential peptide peaks to evaluate their diagnostic accuracy. The identity of peptides corresponding to three representative differential peaks was analyzed. RESULTS: The fewest statistically significant differential peaks were identified between DLBP and CLBP (3), followed by CLBP vs. N (5), DLBP vs. N (9), LDH vs. CLBP (20), DLBP vs. LDH (23), and LDH vs. N (43). The discriminative ability of two most significantly differential peaks was poor in classifying DLBP vs. CLBP but good in classifying DLBP vs. LDH. The accuracy of models for classification of DLBP vs. CLBP was not very high in the blind test (forecasting ability, 67.24%; sensitivity, 70%), although a higher accuracy was observed for classification of DLBP vs. LDH and LDH vs. N (forecasting abilities, ~90%; sensitivities, >90%). A further investigation of three representative differential peaks led to the identification of two peaks as peptides of complement C3, and one peak as a human fibrinogen peptide. CONCLUSIONS: Our findings benefit not only the diagnosis of CLBP but also the understanding of the differences between different forms of DLBP. The ability to distinguish between different causes of CLBP and the identification of serum biomarkers may be of great value to diagnose different causes of DLBP and predict treatment efficacy.