Liangping Li

STUDY DESIGN: Systematic review and meta-analysis. BACKGROUND: Posterolateral fusion (PLF) and posterior lumbar interbody fusion (PLIF) were widely used in the treatment of lumbar isthmic spondylolisthesis (IS). There was a great controversy over the preferred fusion method. OBJECTIVE: The purpose of this study is to evaluate the clinical outcomes between PLF and PLIF for the treatment of IS. MATERIALS AND METHODS: Related studies that compared the clinical effectiveness of PLIF and PLF for the treatment of IS were acquired by a comprehensive search in 4 electronic databases (PubMed, EMBASE, Cochrane Controlled Trial Register, and MEDLINE) from January 1950 through December 2014. Included studies were performed according to eligibility criteria. The main endpoints included: improvement of clinical satisfaction, complication rate, reoperation rate, fusion rate, and reoperation rate. RESULTS: A total of 9 studies were included in the meta-analysis; 6 were low-quality evidence and 2 were high-quality evidence as indicated by the Jadad scale. Compared with PLIF, PLF patients showed lower fusion rates [P=0.005, odds ratio (OR)=0.29 (0.14, 0.58)] and shorter operation times [P<0.00001, weighted mean difference (WMD)=-0.5(-0.61, -0.39)]. No significant difference was found in the term of postoperative visual analogue scale leg score [P=0.92, WMD=0.02 (-0.39, 0.44)] and visual analogue scale back score [P=0.41, WMD=0.20 (-0.28, 0.68)], blood loss [P=0.39, WMD=121.17 (-152.68, 395.01)], complication rate [P=0.42, OR=1.50 (0.56, 4.03)], postoperative Oswestry Disability Index [P=0.3, WMD=1.09 (-0.97, 3.15)], and postoperative clinical satisfaction [P=0.84, OR=1.06 (0.60, 1.86)]. CONCLUSIONS: In conclusion, our meta-analysis suggested that PLF shows significant lower fusion rate compared with PLIF. Although PLIF had more operation time than PLF, there was no significant difference in global assessment of clinical outcome between the 2 fusion procedures. However, future well-designed, randomized-controlled trials are still needed to further confirm our results.

Abstract Recently, microRNAs (miRNAs) have been identified as key regulators of the proliferation and differentiation of mesenchymal stem cells (MSCs). Our previous in vivo study and other in vitro studies using miRNA microarrays suggest that miR-424 is involved in the regulation of bone formation. However, the role and mechanism of miR-424 in bone formation still remain unknown. Here, we identified that the downregulation of miR-424 mediates bone formation under oxidative stress, and we explored its underlying mechanism. Our results showed that miR-424 was significantly downregulated in an anterior lumbar interbody fusion model of pigs and in a cell model of oxidative stress induced by H 2 O 2 . The overexpression of miR-424 inhibited proliferation and osteogenic differentiation shown by a decrease in alkaline phosphatase (ALP) activity, mineralization and osteogenic markers, including RUNX2 and ALP, whereas the knockdown of miR-424 led to the opposite results. Moreover, miR-424 exerts its effects by targeting FGF2. Furthermore, we found that FOXO1 suppressed miR-424 expression and bound to its promoter region. FOXO1 enhanced proliferation and osteogenic differentiation in part through the miR-424/FGF2 pathway. These results indicated that FOXO1-suppressed miR-424 regulates both the proliferation and osteogenic differentiation of MSCs via targeting FGF2, suggesting that miR-424 might be a potential novel therapeutic strategy for promoting bone formation.

In the human body, joint cartilage is of great importance. It has long been a big therapeutic problem to fix joint cartilage lesions as it appears due to different conditions. Recent stories have shown that the cartilage replacement process must delay the extracellular (ECM) cartilage deterioration and modulate the host's inflammation response. For the reconstruction of the articular cartilage, drug-loaded injectable hydrogels were developed. This hydrogel could retain the chondrocyte phenotype, but the host's inflammatory reaction could also be controlled. The bioglass (BG)/sodium alginate (SA) injectable hydrogels was combined with agarose (AG)/Naringin hydrogel in injectable thermal response for articular cartilage regeneration with a non-chargeable hydrogel that contains both Naringin and BG (Naringin–BG hydrogels). The Naringin–BG hydrogel has an adequate swelling ratio that encourages the fusion of tissue formed with host tissue and enables the gradual release of Naringin bioavailabilities enhanced in situ. The Naringin–BG hydrogel can upgrade the typical chondrocyte phenotype by upregulating aggrecan, SRY-box 9, and collagen type II alpha one chain. It may also stimulate the polarization of M2 macrophage, lower inflammations, and prevent ECM degradations through the decrease of the expressions of the indictable metalloproteinase-13 matrix, nitric oxide synthase, and metalloproteinase-1 matrix. The formed tissues were identical to normal tissues and firmly incorporated with the surrounding tissue after administering the Naringin–BG hydrogels into the rat model articular cartilage defects. Then the injectable Naringin–BG hydrogel increases the bioavailable content of Naringin and retains the chondrocyte phenotype.

Aims: Emerging evidence suggests that the pathogenesis of osteoporosis, characterized by impaired osteogenesis, is shifting from estrogen centric to oxidative stress. Our previous studies have shown that the zinc-finger transcription factor krüppel-like factor 5 (KLF5) plays a key role in the degeneration of nucleus pulposus and cartilage. However, its role in osteoporosis remains unknown. We aimed to investigate the effect and mechanism of KLF5 on osteogenesis under oxidative stress. Results: First, KLF5 was required for osteogenesis and stimulated osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). KLF5 was hypermethylated and downregulated in ovariectomy-induced osteoporosis mice and in BMSCs treated with H 2 O 2 . Interestingly, DNA methyltransferases 3B (DNMT3B) upregulation mediated the hypermethylation of KLF5 induced by oxidative stress, thereby impairing osteogenic differentiation. The inhibition of KLF5 hypermethylation using DNMT3B siRNA or 5-AZA-2-deoxycytidine (5-AZA) protected osteogenic differentiation of BMSCs from oxidative stress. Regarding the downstream mechanism, KLF5 induced β-catenin expression. More importantly, KLF5 promoted the nuclear translocation of β-catenin, which was mediated by the armadillo repeat region of β-catenin. Consistently, oxidative stress-induced KLF5 hypermethylation inhibited osteogenic differentiation by reducing the expression and nuclear translocation of β-catenin. Innovation: We describe the novel effect and mechanism of KLF5 on osteogenesis under oxidative stress, which is linked to osteoporosis for the first time. Conclusion: Our results suggested that oxidative stress-induced hypermethylation of KLF5 mediated by DNMT3B impairs osteogenesis by diminishing the interaction with β-catenin, which is likely to contribute to osteoporosis. Targeting the hypermethylation of KLF5 might be a new strategy for the treatment of osteoporosis. Antioxid. Redox Signal. 35, 1–20.