In vitro stretch modulates mitochondrial dynamics and energy metabolism to induce smooth muscle differentiation in mesenchymal stem cells

The FASEB Journal, Год журнала: 2025, Номер 39(2)

Опубликована: Янв. 22, 2025

Abstract The smooth muscle cells (SMCs) located in the vascular media layer are continuously subjected to cyclic stretching perpendicular vessel wall and play a crucial role remodeling blood pressure regulation. Mesenchymal stem (MSCs) promising tools differentiate into SMCs. Mechanical stretch loading offers an opportunity guide MSC‐SMC differentiation mechanical adaption for function regeneration of vessels. This study shows that induces expression SMC markers α‐SMA SM22 MSCs. These exhibit contractile ability vitro facilitate angiogenesis Matrigel plug assay vivo. contraction SMCs requires their energy metabolism. However, underlying mechanism MSCs remains be revealed. Cyclic training promotes glycolysis, oxidative phosphorylation, mitochondrial fusion modulates dynamics‐related proteins (MFN1, MFN2, DRP1) expression, thereby contributing differentiation. Yes‐associated protein (YAP) affects dynamics, glycolysis regulate stretch‐mediated Additionally, Piezo‐type mechanosensitive ion channel component 1 (Piezo1) impacts metabolism by regulating intracellular Ca 2+ levels YAP nuclear localization. It indicates can integrate force signals

Язык: Английский

---

SLC29A1 and SLC29A2 are human nicotinamide cell membrane transporters

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Янв. 30, 2025

Nicotinamide (NAM), a main precursor of NAD+, is essential for cellular fuel respiration, energy production, and other processes. Transporters precursors NAD+ such as nicotinic acid nicotinamide mononucleotide (NMN) have been identified, but the transporter has not elucidated. Here, we demonstrate that equilibrative nucleoside 1 2 (ENT1 2, encoded by SLC29A1 2) drive uptake establish metabolism homeostasis. In addition, ENT1/2 exhibits strong capacity to change metabolite composition transcript, especially those related nicotinamide. We further observe regulates respiration senescence, contributing altering pool level mitochondrial status. Changes status senescence knockdown are reversed NMN supplementation. Together, ENT1 ENT2 act both nicotinamide-level keepers biological regulators through their NAM transport functions. an with crucial roles in production. authors show transporters ENT2), genes SLC29A2, function into cells.

Язык: Английский

---

An Injectable Composite Hydrogel Enhances Bone Regeneration by Rescuing Impaired Mitochondrial Biogenesis and Fusion of BMSCs under Inflammatory Conditions

ACS Applied Polymer Materials, Год журнала: 2025, Номер unknown

Опубликована: Фев. 13, 2025

The treatment of severe bone defects remains an unresolved clinical challenge. Injectable hydrogels loaded with drugs or growth factors are considered to offer substantial benefits in the regeneration irregular shapes under complex pathological microenvironments. In this study, all-silk-derived composite hydrogel was developed for regeneration. methacrylated silk fibroin (SilMA) fabricated situ injection and photocuring serve as a supporting matrix, incorporation platelet-rich plasma (PRP) promote migration pre-differentiation marrow mesenchymal stem cells (BMSCs) during early stage, (SF) microspheres encapsulating berberine (BBR) regulate BMSCs osteogenesis over extended period. were demonstrated by upregulating mitochondrial biogenesis fusion. Additionally, it indicated that impaired osteogenic activity dynamics inflammatory conditions can be reversed through addition SF-BBR microspheres. Rat calvarial defect repair experiments using showed remarkable increase local quantity. These findings suggest SilMA compositing PRP shows great potential modulating function.

Язык: Английский

---

Focal Adhesion Kinase Alleviates Simulated Microgravity-Induced Inhibition of Osteoblast Differentiation by Activating Transcriptional Wnt/β-Catenin-BMP2-COL1 and Metabolic SIRT1-PGC-1α-CPT1A Pathways

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(4), С. 1669 - 1669

Опубликована: Фев. 15, 2025

The metabolic poise, or balance, between glycolysis and fatty acid oxidation (FAO) has recently been found to play a critical role in osteogenic differentiation homeostasis. While simulated microgravity (SMG) is known impede osteoblast (OBD) by inhibiting the Wnt/β-catenin pathway, how it affects metabolism this context remains unclear. We previously analyzed effect of SMG on pre-osteoblast MC3T3-E1 cells that reduced focal adhesion kinase (FAK) activity. This, turn, downregulated two its downstream targets for OBD bone morphogenic protein-2 (BMP2) type-1 collagen (COL1) formation, leading reduction alkaline phosphatase (ALP) activity cell matrix mineralization. In study, we further SMG-induced alterations energy contribute inhibition cells. Consistent with our earlier findings, demonstrated inhibits downregulating collective FAK Wnt/β-catenin-BMP2-COL1 transcriptional pathway. Interestingly, observed also reduces abundance sirtuin-1 (SIRT1), peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) carnitine palmitoyl transferase-1α (CPT1A), which are all key factors regulating mitochondrial number FAO capacity. Accordingly, content potential were lower upon exposure but both rescued administration activator cytotoxic necrotizing factor-1 (CNF1), thereby allowing overcome OBD. Taken together, study indicates regulator SIRT1 may be new target reversing loss.

Язык: Английский

---

Inhibiting angiogenesis and osteogenesis by targeted regulation of KLK4 via the exosomal MiR-422a derived from bone mesenchymal stem cells

Biotechnology and Bioprocess Engineering, Год журнала: 2025, Номер unknown

Опубликована: Март 4, 2025

Язык: Английский

---