Tanshinone IIA attenuates osteoarthritis via inhibiting aberrant angiogenesis in subchondral bone.

Excessive angiogenesis in subchondral bone is a pathological feature of osteoarthritis (OA). Tanshinone IIA (TIIA), an active compound found in Salvia miltiorrhiza, demonstrates significant anti-angiogenic properties. However, the effect of TIIA on abnormal subchondral angiogenesis in OA is still unclear. This study aims to investigate the mechanism of TIIA in modulating subchondral bone angiogenesis during OA and assess its therapeutic potential in OA. Our findings demonstrate that TIIA attenuated articular cartilage degeneration, normalized subchondral bone remodeling, and effectively suppressed aberrant angiogenesis within subchondral bone in monosodium iodoacetate (MIA)-induced OA mice. Additionally, the angiogenesis capacity of primary CD31hiEmcnhi endothelial cells was observed to be significantly reduced after treatment with TIIA in vitro. Mechanically, TIIA diminished the proportion of hypertrophic chondrocytes, ultimately leading to a substantial reduction in the secretion of vascular endothelial growth factor A (VEGFA). The supernatant of hypertrophic chondrocytes promoted the tube formation of CD31hiEMCNhi endothelial cells, whereas TIIA inhibited this process. Furthermore, TIIA effectively suppressed the expression of vascular endothelial growth factor receptor 2 (VEGFR2) along with its downstream MAPK pathway in CD31hiEmcnhi endothelial cells. In conclusion, our data indicated that TIIA could effectively inhibit the abnormal angiogenesis in subchondral bone during the progression of OA by suppressing the VEGFA/VEFGR2/MAPK pathway. These findings significantly contribute to our understanding of the abnormal angiogenesis in OA and offer a promising therapeutic target for OA treatment.

Age-related accumulation of advanced oxidation protein products promotes osteoclastogenesis through disruption of redox homeostasis.

Enhanced osteoclastogenesis is one of the major causes of age-related bone loss. Aging is accompanied by accumulation of advanced oxidation protein products (AOPPs). However, whether AOPPs accumulation contributing to the osteoclastogenesis with aging remains unclear. Here, we showed that AOPPs accumulation was associated with the enhanced osteoclastogenesis and deterioration of bone microstructure in aged mice. In vitro, AOPPs directly induced osteoclastogenesis by interaction with receptor activator of nuclear factor κ B (RANK) and the receptor for advanced glycation end products (RAGE) in the primary bone marrow monocytes. Bindings of AOPPs to RANK and RAGE were able to activate nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, trigger generation of reactive oxygen species, then induce phosphorylation of mitogen-activated protein kinases and c-fos, upregulation of the nuclear factor of activated T cell c1, eventually induce bone marrow monocytes to differentiate into mature osteoclasts. Chronic exposure to AOPPs enhanced osteoclastogenesis and bone loss in mice, which could be alleviated by NADPH oxidase inhibitor apocynin. Local injection of AOPPs into subperiosteal area induced bone resorption at the site of administration, which was similar to the effect of RANK ligand. Together, these results suggested that AOPPs could serve as a novel regulator of osteoclastogenesis and AOPPs accumulation might play an important role in the development of age-related bone loss.

Is anterior decompression and fusion superior to laminoplasty for cervical myelopathy due to ossification of posterior longitudinal ligament? A systematic review and meta-analysis.

Context: Considerable controversy exists over surgical procedures for ossification of the posterior longitudinal ligament (OPLL).Objective: The purpose of the meta-analysis was to compare the clinical outcome of anterior decompression and fusion (ADF) with laminoplasty (LAMP) in treatment of cervical myelopathy due to OPLL.Methods: PubMed, EMBASE and the Cochrane Register of Controlled Trials database were searched to identify potential clinical studies compared ADF with LAMP for cervical myelopathy owing to OPLL. We also manually searched the reference lists of articles and reviews for possible relevant studies. Thirteen studies with 1120 patients were included in our analysis. Subgroup analyses were performed by the canal occupying ratio of OPLL.Results: Overall, the mean preoperative Japanese Orthopaedic Association (JOA) score was similar between two groups. Compared with LAMP group, ADF group was higher at the mean postoperative JOA scores and mean recovery rate, reoperation rate, and longer at mean operation time. There was not significantly different in mean blood loss and complication rate between two groups. In subgroup analysis, ADF had a higher mean postoperative JOA score and recovery rate than LAMP in cases of OPLL with occupying ratios ≥ 50%, while those difference were not found in cases of OPLL with occupying ratios < 50%.Conclusion: ADF achieves better neurological improvement compared with LAMP in treatment of cervical myelopathy due to OPLL, especially in cases of OPLL with occupying ratios ≥ 50%. Complication rate is similar between two groups, but ADF can increase the risk of reoperation.

Two Bariatric Surgical Procedures Differentially Alter the Intestinal Microbiota in Obesity Patients.

AIMS: To explore the intestinal microbiota composition affected by the two most widely used procedures of bariatric surgery, laparoscopic sleeve gastrectomy (LSG) and laparoscopic roux-en-Y gastric bypass (LRYGB), in Chinese obesity patients. METHODS: Stool samples were collected from the obese patients before (n = 87) and with follow-up after the surgery (n = 53). After DNA extraction, 16S rDNA (V3 + V4 regions) sequencing was completed on Illumina HiSeq 2500 sequencing platform. The samples were analyzed base on four groups, pre-LSG (n = 54), pre-LRYGB (n = 33), post-LSG (n = 33), and post-LRYGB (n = 20). The linear mixed models were used to analyze the alteration of intestinal microbiota before and after the surgeries of LSG or LRYGB. Student's t test and χ2 test were used for analysis of independent groups; Metastats analysis was used to compare the relative abundance of bacteria, and Pearson correlation and Spearman correlation analysis were used to test the correlation between indicated groups. RESULTS: 87 patients were included and 53 (60.92%) of them completed the follow-up (9.60 ± 3.92 months). Body mass index (BMI) decreased from 37.84 ± 6.16 kg/m2 to 26.22 ± 4.33 kg/m2 after LSG and from 45.75 ± 14.26 kg/m2 to 33.15 ± 10.99 kg/m2 after LRYGB. The relative abundance of 5 phyla and 42 genera were altered after the surgery in the cohort. Although no alteration of Firmicutes was observed at phylum level, 54.76% of the altered genera belong to phylum Firmicutes. Both LSG and LRYGB procedures increased the richness and evenness of intestinal microbiota in obese patients after the surgery. Particularly, 33 genera altered after LSG and 19 genera altered after LRYGB, in which 11 genera were common alterations in both procedures. CONCLUSION: Both LSG and LRYGB altered the composition of intestinal microbiota in Chinese obesity patients, and particularly increased the richness and evenness of microbiota. Genera belonging to phylum Firmicutes were the most altered bacteria by bariatric surgery. The procedure of LSG resulted in much more pronounced alteration of the intestinal microbiota abundance than that observed in LRYGB. While different genera were altered after LSG and LRYGB procedures, 10 genera were the common altered genera in both procedures. Bacteria altered after LSG and LRYGB were functionally associated with BMI, and with relieving of the metabolic syndromes.

Surgical outcomes of cervical myelopathy due to ossification of posterior longitudinal ligament: Anterior decompression and fusion versus posterior laminoplasty.

BACKGROUND: The purpose of this study was to compare the surgical outcomes of anterior decompression and fusion (ADF) with that of posterior laminoplasty (LAMP) for cervical myelopathy caused by ossification of posterior longitudinal ligament (OPLL). METHODS: We retrospectively assessed the medical records of patients who underwent surgery for cervical myelopathy owing to OPLL between 2007 and 2016 at our institution. Fifty patients were included in this study, including 17 patients in ADF group and 33 patients in LAMP group. Surgical outcomes were assessed under the Japanese Orthopaedic Association (JOA) score. The radiologic and clinical data were compared between two groups. RESULTS: There was no significant difference in age, follow-up time, operation time, blood loss, length of stay, preoperative JOA score, occupying ratio of OPLL, diameter of spinal canal, preoperative and final follow-up C2-C7 Cobb angles, and the change of C2-C7 Cobb angle before and after operation between ADF and LAMP groups. The final follow-up JOA score and the neurological recovery rate were significantly higher in ADF group than in LAMP group, particularly in patients with segmental-type OPLL. Cerebrospinal fluid leakage is a major complication after ADF, C5 paralysis, and axial pain frequently results from LAMP. CONCLUSION: Compared with LAMP, ADF shows better improvement of neurological function in patients with cervical myelopathy due to OPLL, especially in patients with segmental-type cervical OPLL.

Reoperation After Cervical Disc Arthroplasty Versus Anterior Cervical Discectomy and Fusion: A Meta-analysis.

BACKGROUND: Anterior cervical discectomy and fusion is a standard surgical treatment for cervical radiculopathy and myelopathy, but reoperations sometimes are performed to treat complications of fusion such as pseudarthrosis and adjacent-segment degeneration. A cervical disc arthroplasty is designed to preserve motion and avoid the shortcomings of fusion. Available evidence suggests that a cervical disc arthroplasty can provide pain relief and functional improvements similar or superior to an anterior cervical discectomy and fusion. However, there is controversy regarding whether a cervical disc arthroplasty can reduce the frequency of reoperations. QUESTIONS/PURPOSES: We performed a meta-analysis of randomized controlled trials (RCTs) to compare cervical disc arthroplasty with anterior cervical discectomy and fusion regarding (1) the overall frequency of reoperation at the index and adjacent levels; (2) the frequency of reoperation at the index level; and (3) the frequency of reoperation at the adjacent levels. METHODS: PubMed, EMBASE, and the Cochrane Register of Controlled Trials databases were searched to identify RCTs comparing cervical disc arthroplasty with anterior cervical discectomy and fusion and reporting the frequency of reoperation. We also manually searched the reference lists of articles and reviews for possible relevant studies. Twelve RCTs with a total of 3234 randomized patients were included. Eight types of disc prostheses were used in the included studies. In the anterior cervical discectomy and fusion group, autograft was used in one study and allograft in 11 studies. Nine of 12 studies were industry sponsored. Pooled risk ratio (RR) and associated 95% CI were calculated for the frequency of reoperation using random-effects or fixed-effects models depending on the heterogeneity of the included studies. A funnel plot suggested the possible presence of publication bias in the available pool of studies; that is, the shape of the plot suggests that smaller negative or no-difference studies may have been performed but have not been published, and so were not identified and included in this meta-analysis. RESULTS: The overall frequency of reoperation at the index and adjacent levels was lower in the cervical disc arthroplasty group (6%; 108/1762) than in the anterior cervical discectomy and fusion group (12%; 171/1472) (RR, 0.54; 95% CI, 0.36-0.80; p = 0.002). Subgroup analyses were performed according to secondary surgical level. Compared with anterior cervical discectomy and fusion, cervical disc arthroplasty was associated with fewer reoperations at the index level (RR, 0.50; 95% CI, 0.37-0.68; p < 0.001) and adjacent levels (RR, 0.52; 95% CI, 0.37-0.74; p < 0.001). CONCLUSIONS: Cervical disc arthroplasty is associated with fewer reoperations than anterior cervical discectomy and fusion, indicating that it is a safe and effective alternative to fusion for cervical radiculopathy and myelopathy. However, because of some limitations, these findings should be interpreted with caution. Additional studies are needed. LEVEL OF EVIDENCE: Level I, therapeutic study.