Adipocyte cell death is pathologically involved in both obesity and lipodystrophy. Inflammation and pro-inflammatory cytokines are generally regarded as inducers for adipocyte apoptosis, but whether some innate defects affect their susceptibility to cell death has not been extensively studied. Here, we found bone morphogenetic protein receptor type 2 (BMPR2) knockout adipocytes were prone to cell death, which involved both apoptosis and pyroptosis. BMPR2 deficiency in adipocytes inhibited phosphorylation of perilipin, a lipid-droplet-coating protein, and impaired lipolysis when stimulated by tumor necrosis factor (TNFα), which lead to failure of fatty acid oxidation and oxidative phosphorylation. In addition, impaired lipolysis was associated with mitochondria-mediated apoptosis and pyroptosis as well as elevated inflammation. These results suggest that BMPR2 is important for maintaining the functional integrity of adipocytes and their ability to survive when interacting with inflammatory factors, which may explain why adipocytes among individuals show discrepancy for death responses in inflammatory settings.

Adipocyte apoptosis is a normal process for adipose tissue self-renewal, however overt apoptosis is pathologically involved in both obesity and lipodystrophy. Pro-inflammatory cytokines are generally regarded as inducers for adipocyte apoptosis, but whether some innate defects of adipocytes affect their apoptotic susceptibility has rarely been studied. Here, we found BMPR2 knockout adipocytes were prone to TNFα-induced apoptosis both in vivo and ex vivo. BMPR2 deficiency in adipocytes inhibited phosphorylation of lipid-droplet-coating protein, perilipin, and impaired lipolysis stimulated by TNFα. Impaired lipolysis failed to supply fatty acid for mitochondrial oxidation, oxidative phosphorylation and stimulated mitochondria-mediated apoptosis. These results suggest that the innate functional integrity of adipocytes determines their ability to survive when interacting with inflammatory factors, which may explain why adipocytes among individuals show discrepancy for apoptotic responses to the same inflammatory pressure.Funding: This study was supported by the National Natural Science Foundation of China (grant no. 31670787 to S.W.Q. and 31571471 to Q.Q.T.), the Ministry of Science and technology of China grant (2013CB530601 to Q.Q.T), and the State Key Program of National Natural Science Foundation of China (grant no. 81390353 to Q.Q.T.). The research was partially supported by 985 Project (985-YFX0302).Declaration of Interest: All authors have no competing interests to declare, financial or otherwise.Ethical Approval: This study was approved by the ethics committees of Shanghai Medical College, Fudan University and was in accordance with the principle of the Helsinki Declaration II. The written informed consent was obtained from each participant.

Objectives: To assess risk factors, outcomes and provide combinations of treatment for placenta accreta in our hospital of Shanghai, China. Methods: Clinical data of 153 women with placenta accreta and 149 controls between January 2010 and January 2015 were retrospectively collected. Univariate and multivariable logistic regression analyses were performed. Results: The maternal age (OR = 1.268, 95% CI: 1.143-1.406), gravidity (twice, OR = 3.435, 95% CI: 1.413-8.350; 3 times, OR = 9.643, 95% CI: 3.901-23.838) and low-lying placenta (OR = 15.952, 95% CI: 4.701-54.127) were independent risk factors for placenta accreta. Postpartum hemorrhage was the main complication in patients with placenta accreta, leading to the requirement for conservative treatments by intrauterine packing with gauze (15, 33.3%)/water bag (15, 9.8%), B-Lynch suture (9, 5.9%), uterine arterial embolization (14, 9.2%), ligation of the ascending branch of the uterine artery (4, 2.6%) intraoperatively, and injection of MTX (105, 68.6%) postoperatively. Neonates born to women with placenta accreta had significantly lower birth weight, Apgar scores at 5 min and higher rates of neonatal asphyxia, but no deaths occurred. Conclusion: Planned delivery and intervention is necessary for women with placenta previa, multiple gravidity and advanced maternal age to prevent adverse outcomes.

The poor healing potential of intra-articular ligament injuries drives a need for the development of novel, viable ‘neo-ligament’ alternatives. Ex vivo approaches combining stem cell engineering, 3-dimensional biocompatible scaffold design and enhancement of biological and biomechanical functionality via the introduction of key growth factors and morphogens, represent a promising solution to ligament regeneration. We investigated growth, differentiation and extracellular matrix (ECM) protein production of human adipose-derived mesenchymal stem/stromal cells (MSCs), cultured in 5% human platelet lysate (PL) and seeded on three-dimensional polycaprolactone (PCL) scaffolds, in response to the connective-tissue related ligands fibroblast growth factor 2 (basic) (FGF2) and growth and differentiation factor-5 (GDF5). Phenotypic alterations of MSCs under different biological conditions were examined using cell viability assays, real time qPCR analysis of total RNA, as well as immunofluorescence microscopy. Phenotypic conversion of MSCs into ECM producing fibroblastic cells proceeds spontaneously in the presence of human platelet lysate. Administration of FGF2 and/or GDF5 enhances production of mRNAs for several ECM proteins including Collagen types I and III, as well as Tenomodulin (e.g., COL1A1, TNMD), but not Tenascin-C (TNC). Differences in the in situ deposition of ECM proteins Collagen type III and Tenascin-C were validated by immunofluorescence microscopy. Treatment of MSCs with FGF2 and GDF5 was not synergistic and occasionally antagonistic for ECM production. Our results suggest that GDF5 alone enhances the conversion of MSCs to fibroblastic cells possessing a phenotype consistent with that of connective-tissue fibroblasts.