Role of Hedgehog Signaling Pathways in Multipotent Mesenchymal Stem Cells Differentiation.

Multipotent mesenchymal stem cells (MSCs) have high self-renewal and multi-lineage differentiation potentials and low immunogenicity, so they have attracted much attention in the field of regenerative medicine and have a promising clinical application. MSCs originate from the mesoderm and can differentiate not only into osteoblasts, cartilage, adipocytes, and muscle cells but also into ectodermal and endodermal cell lineages across embryonic layers. To design cell therapy for replacement of damaged tissues, it is essential to understand the signaling pathways, which have a major impact on MSC differentiation, as this will help to integrate the signaling inputs to initiate a specific lineage. Hedgehog (Hh) signaling plays a vital role in the development of various tissues and organs in the embryo. As a morphogen, Hh not only regulates the survival and proliferation of tissue progenitor and stem populations but also is a critical moderator of MSC differentiation, involving tri-lineage and across embryonic layer differentiation of MSCs. This review summarizes the role of Hh signaling pathway in the differentiation of MSCs to mesodermal, endodermal, and ectodermal cells.

Characterization of a Type VI Secretion System vgrG2 Gene in the Pathogenicity of Burkholderia thailandensis BPM.

Burkholderia thailandensis is a clinically underestimated conditional pathogen in the genus Burkholderia, the pathogenicity of the infection caused by B. thailandensis remains poorly understood. According to previous studies, Type-VI secretion system (T6SS) is a protein secreting device widely existing in Gram-negative bacilli. Valine-glycine repeat protein G (VgrG) is not only an important component of T6SS, but also a virulence factor of many Gram-negative bacilli. In one of our previous studies, a unique T6SS vgrG gene (vgrG2 gene) was present in a virulent B. thailandensis strain BPM (BPM), but not in the relatively avirulent B. thailandensis strain E264 (E264). Meanwhile, transcriptome analysis of BPM and E264 showed that the vgrG2 gene was strongly expressed in BPM, but not in E264. Therefore, we identified the function of the vgrG2 gene by constructing the mutant and complemented strains in this study. In vitro, the vgrG2 gene was observed to be involved in the interactions with host cells. The animal model experiment showed that the deletion of vgrG2 gene significantly led to the decrease in the lethality of BPM and impaired its ability to trigger host immune response. In conclusion, our study provides a new perspective for studying the pathogenicity of B. thailandensis and lays the foundation for discovering the potential T6SS effectors.

Gene expression regulations by long noncoding RNAs and their roles in cancer.

Cancers are deadly diseases. The general mystery of carcinogenesis, primary and acquired drug resistance and distant organ metastasis are still puzzles to be solved. Long noncoding RNAs (lncRNAs) are receiving more and more attention in recent years since their roles in transcriptional regulation have been unveiled. Detailed functional annotations of lncRNAs have showed that their regulatory roles are largely determined by their binding partners. LncRNAs directly bind to DNA, RNA and proteins and regulate gene expression at transcriptional, post-transcriptional and post-translational levels. Here we review the current understanding of molecular functions of lncRNAs, will emphasize on their binding partners and summarize their biological roles in cancer.

Debridement, antibiotics, and implant retention for periprosthetic knee infections: a pooling analysis of 1266 cases.

BACKGROUND: The debridement, antibiotics, and implant retention (DAIR) procedure is an established therapeutic option for periprosthetic knee infections (PKI). However, the efficacy and the indication for this procedure are still controversial. METHODS: All the relevant literatures were systematically reviewed and analyzed. The present study aimed to assess the success rate of DAIR in the management of PKI, identify the factors associated with prognosis of DAIR, and establish a simple algorithm for predicting a high success rate of DAIR. RESULTS: Totally, 33 studies with 1266 cases were included. The overall success rate following DAIR in the management of PKI was 57.11%. In the subgroup analyses, the factors of "the time from symptoms to debridement was < 3 weeks" and "the bacterial species other than methicillin-resistant Staphylococcus aureus" significantly improved the success rate of DAIR and thus were defined as the major criteria. The statistically insignificant factors of "the open debridement and liner exchange" and "the comorbidity of rheumatoid arthritis" were set as the minor criteria. The success rate of DAIR for PKI meeting all the major criteria and no less than one minor criterion was 80.98%, which was significantly higher than the overall success rate of DAIR (p < 0.05). CONCLUSION: PKI cases meeting two major criteria and no less than one minor criterion may confer a high success rate of DAIR. This simple algorithm may contribute to identifying the appropriate PKI patient for DAIR treatment and predicting the prognosis of DAIR.

Mechanical Properties and Porosity of Acrylic Cement Bone Loaded with Alendronate Powder.

Aseptic loosening is the most common complication of joint replacement. Previous studies showed that acrylic bone cement loaded with a commercially-available alendronate powder (APAC) had good promise against wear debris-mediated osteolysis for prevention of aseptic loosening. The purpose of the present study was to investigate the effect of adding alendronate powder to an acrylic bone cement on quasi-static mechanical properties (namely, compressive strength, compressive modulus, tensile strength, and flexural strength), fatigue life, porosity, and microstructure of the cement. The results showed that adding up to 1 wt./wt.% alendronate powder exerted no detrimental effect on any of the quasi-static mechanical properties. However, the fatigue life of APAC decreased by between ~17% and ~27 % and its porosity increased by between ~ 5-7 times compared with corresponding values for the control cement (no alendronate powder added). Fatigue life was negatively and significantly correlated with porosity. Considering that fatigue life of the cement plays a significant role in joint replacement survival, clinical use of APAC cannot be recommended.

Microbubble-Mediated Ultrasound Outweighs Low-Intensity Pulsed Ultrasound on Osteogenesis and Neovascularization in a Rabbit Model of Steroid-Associated Osteonecrosis.

Microbubbles magnify the acoustic pressure of low-intensity pulsed ultrasound (LIPUS) and may enhance its bioeffect for diagnostic and therapeutic purposes. This study compared the effect of this novel microbubble-mediated ultrasound (MUS) with that of the traditional LIPUS on osteogenesis and neovascularization in a rabbit model of steroid-associated osteonecrosis. We hypothesized that MUS might outweigh LIPUS on promoting osteogenesis and neovascularization in steroid-associated osteonecrosis. The bilateral femoral head necrosis was induced by lipopolysaccharide and methylprednisolone in the rabbits. The indices of bone mineral density (BMD), trabecular number, maximal loading strength, and mineral apposition rate were analyzed, demonstrating that the animal model of steroid-associated osteonecrosis was successfully established. Both the MUS group (GM) and the LIPUS group (GL) were insonated 20 min daily for six weeks. GM received an extra intracapsular injection of microbubbles before insonation every other day. Fluorescence bone labeling, Micro-CT Analysis, biomechanical test, quantitative real-time PCR, Western blot analysis, and histological evaluation were performed for comparing GM with GL. The results demonstrated a 39% higher mineral apposition rate in GM compared with GL. The BMD and the maximal loading strength of femoral head of GM increased by 4.3% and 27.8% compared to those of GL, respectively. The mRNA and protein expression of BMP-2 and VEGF were also significantly higher in GM. The number of blood vessels of GM was 65% greater than that of GL. MUS is more potent than LIPUS in enhancing osteogenesis, neovascularization, and biomechanical strength of femoral head in the animal model of steroid-associated osteonecrosis. Without increasing the intensity of insonation or the risk of tissue damage, MUS is better for inhibiting the process of steroid-associated osteonecrosis.

Squeaking in fourth-generation ceramic-on-ceramic total hip replacement and the relationship with prosthesis brands: meta-analysis and systematic review.

BACKGROUND: Postoperative squeaking in patients who applied the fourth-generation ceramic bearing in primary hip replacement has not been reported systematically; we aim to study the squeaking incidence in the fourth-generation ceramic bearing and related risk factors for squeaking, and we also attempt to explore the relationship between squeaking and prosthetic brands. METHODS: The PubMed, Embase, and Cochrane library were searched, and 14 articles were finally included. Patients' demographic data, surgical-related information, and prosthesis data were extracted. The occurrence rate of squeaking was calculated by meta-analysis, and subgroup analysis was performed based on prosthetic brands and follow-up time. Regression analysis was further applied to investigate the relationship between various risk factors and squeaking. RESULTS: The squeaking incidence in patients with the fourth-generation ceramic bearing was 3%. Age, gender, body mass index, and abduction and anteversion angles of acetabular cup might have no influence on squeaking. The squeaking incidence was significantly high with the presence of Delta Motion cup (DePuy, Warsaw, Indiana) and Secure-Fit stem (Stryker, Kalamazoo, MI), and the overall incidence of DePuy femoral stem was relatively small except for the Summit femoral stem. And there was no significant difference of squeaking incidence between less than 5-year and more than or equal to 5-year follow-up subgroups. CONCLUSIONS: In our study, squeaking in the fourth-generation ceramic bearing occurred at a rate of 3%; occurrence rate was high when the Delta Motion cup was applied. We hope for more relevant researches to focus on this issue.