Foxk1 stimulates adipogenic differentiation via a peroxisome proliferator-activated receptor gamma 2-dependent mechanism.

Adipogenesis is a tightly regulated process, and its dysfunction has been linked to metabolic disorders such as obesity. Forkhead box k1 (Foxk1) is known to play a role in the differentiation of myogenic precursor cells and tumorigenesis of different types of cancers; however, it is not clear whether and how it influences adipocyte differentiation. Here, we found that Foxk1 was induced in mouse primary bone marrow stromal cells (BMSCs) and established mesenchymal progenitor/stromal cell lines C3H/10T1/2 and ST2 after adipogenic treatment. In addition, obese db/db mice have higher Foxk1 expression in inguinal white adipose tissue than nonobese db/m mice. Foxk1 overexpression promoted adipogenic differentiation of C3H/10T1/2, ST2 cells and BMSCs, along with the enhanced expression of CCAAT/enhancer binding protein-α, peroxisome proliferator-activated receptor γ (Pparγ), and fatty acid binding protein 4. Moreover, Foxk1 overexpression enhanced the expression levels of lipogenic factors during adipogenic differentiation in both C3H/10T1/2 cells and BMSCs. Conversely, Foxk1 silencing impaired these cells from fully differentiating. Furthermore, adipogenic stimulation induced the nuclear translocation of Foxk1, which depended on the mTOR and PI3-kinase signaling pathways. Subsequently, Foxk1 is directly bound to the Pparγ2 promoter, stimulating its transcriptional activity and promoting adipocyte differentiation. Collectively, our study provides the first evidence that Foxk1 promotes adipocyte differentiation from progenitor cells by promoting nuclear translocation and upregulating the transcriptional activity of the Pparγ2 promoter during adipogenic differentiation.

Polyzwitterion Manipulates Remineralization and Antibiofilm Functions against Dental Demineralization.

Biomineralization technology has become a trend for the arrest and prevention of dental caries. In particular, the bioactivity and ability to release large amounts of Ca2+ and PO43- ions make amorphous calcium phosphate (ACP) for hard tissue remineralization are highly desired. However, the instability of ACP limits its clinical application. Under continuous bacterial challenge in the oral cavity, the currently developed ACP-based remineralization system lacks the ability to inhibit bacterial adhesion and biofilm formation. Here, a dual-functional nanocomposite with antibiofilm and remineralization properties was designed by combining zwitterionic poly(carboxybetaine acrylamide) (PCBAA) and ACP. The resulting nanocomposite was stable in solution for at least 3 days without any aggregation. The PCBAA/ACP nanocomposite exerted a significant inhibitory effect on the adhesion and biofilm formation of Streptococcus mutans and exhibited bactericidal activities under acidic conditions resulting from bacteria. Moreover, compared with fluoride, this nanocomposite demonstrated superior effects in promoting the remineralization of demineralized enamel and the occlusion of exposed dentinal tubules in vivo and in vitro. The present work provides a theoretical and experimental basis for the use of the PCBAA/ACP nanocomposite as a potential dual-functional agent for arresting and preventing caries.

Surface functionalization of titanium substrates with Deoxyribonuclease I inhibit peri-implant bacterial infection.

This study aimed to investigate the effect of Deoxyribonuclease I (DNase I) coating on initial adhesion and biofilm formation of peri-implant bacteria. Titanium (Ti), Ti-polydopamine (Ti-PDOP), Ti-PDOP-DNase I and Ti-PDOP-inactivated DNase I samples were studied. The FE-SEM, EDS and XPS were used to confirm that DNase I was coated onto Ti. The initial adhesion and biofilm formation of Aggregatibacter actinomycetemcomitans (A.a) and Fusobacterium nucleatum (F.n) were observed by CLSM. The osteogenic induction of Ti-PDOP-DNase I on MC3T3-E1 cells was investigated by ALP activity and RT-PCR. The adhesion clearance rate of viable bacteria on the surfaces of Ti-PDOP-DNase I was 91.95% for A.a, and 96.37% for F.n, and the 24 h biofilm formation of the bacteria was significantly inhibited. In addition, on DNase I coating, the mRNA level of osteogenic marker genes (alp, opn, bsp, sp7) and the activity of ALP were both up-regulated. Therefore, DNase I coating could be an alternative approach for preventing implant-related infection.

Long noncoding RNA Plnc1 controls adipocyte differentiation by regulating peroxisome proliferator-activated receptor γ.

Detailed understanding of molecular mechanisms controlling adipogenesis is of great importance to identify new targets for treating obesity. Emerging evidence suggests that long noncoding RNAs (lncRNAs) may play a pivotal role in adipogenesis. Here, we have identified a novel lncRNA, Plnc1, which is transcribed from a position ∼25,000 bp upstream of the peroxisome proliferator-activated receptor γ2 ( PPAR-γ2) gene. Plnc1 is abundantly expressed in adipose tissue, and obese mice have higher Plnc1 expression in adipose tissue than nonobese mice. Plnc1 was induced in established adipogenic lines ST2, 3T3-L1, and C3H10T1/2 as well as in bone marrow stromal cells (BMSCs) after adipogenic treatment. Plnc1 knockdown blocked differentiation of ST2 cells and BMSCs into mature adipocytes, along with the reduction of PPAR-γ, CCAAT/enhancer binding protein-α, and adipocyte protein 2. Conversely, overexpression of Plnc1 promoted ST2 cells and BMSCs to fully differentiate. Mechanism studies revealed that Plnc1 could reduce the methylation level of CpG region in the PPAR-γ2 promoter and enhance the transcriptional activity of the promoter and thereby increase PPAR-γ2 transcription. Our study suggests that Plnc1 promotes adipogenic differentiation through controlling the key adipogenic transcription factor PPAR-γ and highlights the potential of Plnc1 as a target for new therapies to control metabolic disorders like obesity.-Zhu, E., Zhang, J., Li, Y., Yuan, H., Zhou, J., Wang, B. Long noncoding RNA Plnc1 controls adipocyte differentiation by regulating peroxisome proliferator-activated receptor γ.