Quite a few randomized controlled trials (RCTs) investigating the efficacy of platelet-rich plasma (PRP) for treatment of knee osteoarthritis (OA) have been recently published. Therefore, an updated systematic review was performed to evaluate the temporal effect of PRP on knee pain and physical function. Pubmed, Embase, Cochrane library, and Scopus were searched for human RCTs comparing the efficacy and/or safety of PRP infiltration with other intra-articular injections. A descriptive summary and quality assessment were performed for all the studies finally included for analysis. For studies reporting outcomes concerning Western Ontario and McMaster Universities Arthritis Index (WOMAC) or adverse events, a random-effects model was used for data synthesis. Fourteen RCTs comprising 1423 participants were included. The control included saline placebo, HA, ozone, and corticosteroids. The follow-up ranged from 12 weeks to 12 months. Risk of bias assessment showed that 4 studies were considered as moderate risk of bias and 10 as high risk of bias. Compared with control, PRP injections significantly reduced WOMAC pain subscores at 3, 6, and 12 months follow-up (p = 0.02, 0.004, <0.001, respectively); PRP significantly improved WOMAC physical function subscores at 3, 6, and 12 months (p = 0.002, 0.01, <0.001, respectively); PRP also significantly improved total WOMAC scores at 3, 6 and 12 months (all p < 0.001); nonetheless, PRP did not significantly increased the risk of post-injection adverse events (RR, 1.40 [95% CI, 0.80 to 2.45], I 2 = 59%, p = 0.24). Intra-articular PRP injections probably are more efficacious in the treatment of knee OA in terms of pain relief and self-reported function improvement at 3, 6 and 12 months follow-up, compared with other injections, including saline placebo, HA, ozone, and corticosteroids. PROSPERO CRD42016045410 . Registered 8 August 2016.

Introduction: Stroke is a major cause of permanent neurologic damage, with few effective treatments available to restore lost function. Induced pluripotent stem cells (iPSCs) have the potential to generate all cell types in vitro and can be generated from a stroke patient. Therefore, iPSCs are attractive donor sources of genetically identical “patient-specific” cells to hold promise in therapy for stroke. In the present study, we established a four-stage culture system by using serum-free medium and retinoic acid (RA) to differentiate iPSCs into neural stem cells (NSCs) effectively and stably. Our hypothesis was that iPSC-derived NSCs would survive, migrate, and differentiate in vivo, and improve neurologic function after transplantation into the brains of rats with ischemic stroke. Methods: Human iPSCs (iPS-S-01) and human ESCs (HuES17) were used to differentiate into NSCs by using our four-stage culture system. iPSCs and differentiated NSCs were characterized by immunocytochemistry staining and reverse transcription-polymerase chain reaction (RT-PCR) analysis. After establishment of focal cerebral ischemia with occlusion of the middle cerebral artery (MCA) and cell transplantation, animals were killed at 1 week and 2 weeks to analyze survival, migration, and differentiation of implanted cells in brain tissue. Animal behavior was evaluated via rope grabbing, beam walking, and Morris water maze tests. Results: iPSCs were efficiently induced into NSCs by using a newly established four-stage induction system in vitro. iPSCs expressed pluripotency-associated genes Oct4, Sox2, and Nanog before NSC differentiation. The iPSC-derived NSCs spontaneously differentiated into neurons and astrocytes, which highly express β-tubulin and glial fibrillary acidic protein (GFAP), respectively. On transplantation into the striatum, CM-DiI labeled iPSC-derived NSCs were found to migrate into the ischemia area at 1 week and 2 weeks, and animal-function recovery was significantly improved in comparison with control groups at 3 weeks. Conclusions: The four-stage induction system is stable and effective to culture, differentiate, and induce iPSCs to NSCs by using serum-free medium combined with retinoic acid (RA). Implanted iPSC-derived NSCs were able to survive, migrate into the ischemic brain area to differentiate into mature neural cells, and seem to have potential to restore lost neurologic function from damage due to stroke in a rat model.

Scientific interest in exosomes has exploded in recent decades. In 1990 only three articles were published on exosomes, while over 1,700 have already been published half‐way into 2020.¹ While researchers have shown much interest in exosomes since being discovered in 1981, an appreciation of the potential role of glycans in exosome structure and function has emerged only recently. Glycosylation is one of the most common post‐translational modification, which functions in many physiological and pathological aspects of cellular function. Many components of exosomes are heavily glycosylated including proteins, lipids, among others. Thus, glycosylation undoubtedly has a great impact on exosome biosynthesis and function. Despite the importance of glycosylation in exosomes and the recent recognition of them as biomarkers for not only malignancies but also other system dysfunction and disease, the characterization of exosome glycans remains understudied. In this review, we discuss glycosylation patterns of exosomes derived from various tissues, their biological features, and potential for various clinical applications. We highlight state‐of‐the‐art knowledge about the fine structure of exosomes, which will allow researchers to reconstruct them by surface modification. These efforts will likely lead to novel disease‐related biomarker discovery, purification tagging, and targeted drug transfer for clinical applications in the future.

Aims: Methicillin-resistant Staphylococcus aureus (MRSA) can cause wound infections via a ‘Trojan Horse’ mechanism, in which neutrophils engulf intestinal MRSA and travel to the wound, releasing MRSA after apoptosis. The possible role of intestinal MRSA in prosthetic joint infection (PJI) is unknown.Methods: Rats underwent intestinal colonization with green fluorescent protein (GFP)-tagged MRSA by gavage and an intra-articular wire was then surgically implanted. After ten days, the presence of PJI was determined by bacterial cultures of the distal femur, joint capsule, and implant. We excluded several other possibilities for PJI development. Intraoperative contamination was excluded by culturing the specimen obtained from surgical site. Extracellular bacteraemia-associated PJI was excluded by comparing with the infection rate after intravenous injection of MRSA or MRSA-carrying neutrophils. To further support this theory, we tested the efficacy of prophylactic membrane-permeable and non-membrane-permeable antibiotics in this model.Results: After undergoing knee surgery eight or 72 hours after colonization, five out of 20 rats (25.0%) and two out of 20 rats (10.0%) developed PJI, respectively. Strikingly, 11 out of 20 rats (55.0%) developed PJI after intravenous injection of MRSA-carrying neutrophils that were isolated from rats with intestinal MRSA colonization. None of the rats receiving intravenous injections of MRSA developed PJI. These results suggest that intestinal MRSA carried by neutrophils could cause PJI in our rat model. Ten out of 20 (50.0%) rats treated with non-membrane-permeable gentamicin developed PJI, whereas only one out of 20 (5.0%) rats treated with membrane-permeable linezolid developed PJI.Conclusion: Neutrophils as carriers of intestinal MRSA may play an important role in PJI development. Cite this article: Bone Joint Res. 2020;9(4):152–161.

Osteosarcoma (OS), which affects adolescents especially during a growth spurt, has the highest incidence of any primary malignant bone tumour, and a high rate of early metastasis leading to a very poor prognosis. In recent years, non-coding RNAs, especially long non-coding RNAs (lncRNAs) have attracted more and more attention as novel epigenetic regulators in a variety of tumours, including OS. Most recently, metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) was found to play an important role in OS progression by modulating the enhancers of zeste homolog 2 (EZH2). Furthermore, MALAT1 could inhibit the expression of E-cadherin and promote the expression of β-catenin, and this phenomenon might be the outcome of MALAT1-induced EZH2 activation. In this study, we investigated the vital function of MALAT1 in the progression of OS and its potential leading mechanism, altering the expression and localization of β-catenin via epigenetic transcriptional regulation by interacting with EZH2. With the help of MALAT1 silencing using small interfering RNAs (siRNAs), the loss of E-cadherin of MNNG/HOS cells was rescued, and the abnormal expression and localization of β-catenin were corrected at the same time. Overall, our research showed promising potential for new treatment strategies based on epigenetic regulation targeting MALAT1, which will not only coordinate with the patient's immune system, but also eliminate OS in conjunction with chemotherapy.

Glycosylation is an important modification of membrane proteins that results in functional changes in many cellular activities, from cell-cell recognition to regulatory signaling. Fucosyltransferase 8 (FUT8) is the sole enzyme responsible for core fucosylation, and aberrant fucosylation by dysregulated expression of fucosyltransferases is responsible for the growth of various types of carcinomas. However, the function of FUT8 in the progress of osteosarcoma (OS) has not been reported. In this study, we found that FUT8 is expressed at lower levels in patients with OS and in human OS cell lines such as MNNG/HOS, U2OS, and 143B, suggesting that attenuated expression of FUT8 is involved in the growth and progression of OS. Mechanistically, FUT8 affects the survival strategy of OS by modifying core-fucosylation levels of TNF receptors (TNFRs). Lower fucosylation of TNFRs activates the non-canonical NF-κB signaling pathway, and in turn, decreases mitochondria-dependent apoptosis in OS cells. Together, our results point to FUT8 being a negative regulator of OS that enhances OS-cell apoptosis and suggests a novel therapeutic strategy for treating OS.