Three-dimensional spheroids of mesenchymal stem/stromal cells promote osteogenesis by activating stemness and Wnt/β-catenin.

Mesenchymal stem/stromal cells (MSCs) are multipotent and self-renewal cells that are widely used in regenerative medicine. The culture of three-dimensional (3D) spheroid MSCs more accurately mimics the biological microenvironment. However, it is unclear which key molecules are responsible for the cell fate control of MSCs during 3D spheroid formation and their impact on the functional characteristics of these stem cells. Furthermore, it remains unclear what effects 3D spheroid MSC transplantation has on new bone formation compared with that of 2D monolayer MSCs. We assessed whether the osteogenerative potential of 3D spheroid MSCs is greater than that of 2D monolayer MSCs in vitro. In addition, to elucidate the ability of 3D spheroid MSCs to regenerate bone, we examined the effects of transplanting wild-type (WT) or knockout (KO) spheroid MSCs on new bone formation in mice calvarial defect model in vitro. The 3D spheroid MSC culture dramatically upregulated into stemness markers compared with the 2D monolayer MSC culture. In contrast, BMP-2 significantly increased the osteogenesis-related molecules in the 3D spheroid MSCs but, in turn, downregulated the stemness markers. BMP-2 activated Smad1/5 together with Wnt/β-catenin in 3D spheroid MSCs. Transplantation of these MSCs into aged mice with calvarial defects promoted new bone formation compared with that of 2D monolayer MSCs. In contrast, transplantation of 3D or 2D β-catenin knockout MSCs induced little new bone formation. The 3D spheroid MSC culture had higher stemness compared with the 2D monolayer MSC culture. The culture of 3D spheroid MSCs rapidly promoted osteoblastogenesis and bone formation through synergistic activation of the Wnt/β-catenin pathway in vitro. The transformation of 3D spheroid, but not 2D monolayer, MSCs promoted new bone regeneration in vivo. These results indicate that transplantation of 3D spheroid MSCs in regeneration therapy contributes to a shorter regenerative healing process, including new bone formation.福岡歯科大学2019年

Relationship between family support and nutrient intake status in type 2 diabetes mellitus patients

【目的】通院中の2型糖尿病外来患者を対象に、情動的サポート、行動的サポート、また情報的サポートに着目し、家族による支援の有無別に栄養素等摂取状況の検討を行った。【方法】2016年3月～8月、新潟市Ｂ病院の2型糖尿病外来患者42名（年齢中央値68.0歳、男性比率66.7％）を対象に実施した、自記式質問紙調査及び食物摂取頻度調査データを用いた（有効回答率70.0％）。質問紙調査より得た、家族による支援の有無によって対象者を2群に区分した。食物摂取頻度調査より得たデータを用いて、2群のエネルギー及び栄養素等摂取量、食品群別摂取量（密度法によって調整）についてMann-Whitney のU 検定を用いて検討した。【結果】「食事療法を守っていることをほめる」の問いでは、支援あり7名（16.7％）、支援なし35名（83.3％）であった。2群の1000kcal あたりの栄養素等・食品群別摂取量で差がみられた項目はなかった。「同じ時間に食事をする」の問いでは、支援あり32名（76.2％）、支援なし10名（23.8％）であった。支援ありの者で相対的に、たんぱく質（p＝0.045）、豆類（p＝0.022）摂取量が多く、菓子類（p＝0.020）、油脂類（p＝0.039）の摂取量が少なかった。「家族の糖尿病の知識の有無」では、知識ありの者で油脂類のみ摂取量が相対的に多かった（p＝0.013）。また、「家族の食事療法の知識の有無」では、知識ありの者で嗜好飲料のみ摂取量が相対的に多かった（p＝0.028）。【結論】2 型糖尿病外来患者が受ける家族による支援として、「ほめる」という情動的サポートや疾患や食事療法の知識という情報的サポートに比べ、「同じ時間に食事をする」という家族の存在、家族の行動的サポートが栄養素等摂取状況に関連することが示唆された。Objective: To investigate the relationship between family support, specifically emotional, practical, and informational support, and nutrient intake status in type 2 diabetes mellitus (DM) outpatients. Methods: We distributed a self-report questionnaire and food frequency questionnaire to 42 outpatients with type 2 DM (median age: 68.0 years; men: 66.7%) from a community hospital-based registry in Niigata City between March to August 2016. From the self-report questionnaire, the patients were divided into two groups based on whether they received family support or not. Energy and nutrient intake and intake by food groups were compared using Mann-Whitney U test between the two groups.Results: Regarding the item “Praise for complying with medical nutritional therapy,” 7 patients (16.7%) were praised and 35 patients (83.3%) were not. There was no significant difference in nutrient intake or intake by food group between these two groups. For the item “family eating at the same time,” 32 patients (76.2%) responded that they had family meals together versus 10 patients (23.8%) who did not. Regarding energy and nutrient intake and intake by food group, families who ate together had meals with significantly higher protein (p= 0.045) and beans (p= 0.022) content with less confectionary (p= 0.010) and oil and fat (p= 0.039) content compared with families who did not eat together. Fat and oil intake was significantly higher among families with knowledge of DM and intake of beverage was higher among families with knowledge of dietary treatment than among families without such knowledge. Conclusion: For family support, our findings suggested that practical support such as eating at same time was more strongly related to nutrient intake among type 2 DM patients in comparison with emotional support such as praising patients

Functional annotation of human long noncoding RNAs via molecular phenotyping

Long noncoding RNAs (lncRNAs) constitute the majority of transcripts in the mammalian genomes, and yet, their functions remain largely unknown. As part of the FANTOM6 project, we systematically knocked down the expression of 285 lncRNAs in human dermal fibroblasts and quantified cellular growth, morphological changes, and transcriptomic responses using Capped Analysis of Gene Expression (CAGE). Antisense oligonucleotides targeting the same lncRNAs exhibited global concordance, and the molecular phenotype, measured by CAGE, recapitulated the observed cellular phenotypes while providing additional insights on the affected genes and pathways. Here, we disseminate the largest-todate lncRNA knockdown data set with molecular phenotyping (over 1000 CAGE deep-sequencing libraries) for further exploration and highlight functional roles for ZNF213-AS1 and lnc-KHDC3L-2.Peer reviewe