Energy Metabolism During Osteogenic Differentiation: The Role of Akt.

Stem Cells Dev

Center for Musculoskeletal Research, University of Rochester School of Medicine & Dentistry, Rochester, New York, USA.

Published: February 2021

AI Article Synopsis

  • Researchers studied how osteogenic media and factors like Wnt3a and BMP2 affect energy metabolism in stem cells, finding that they mainly enhance mitochondrial oxidative phosphorylation (OxPhos) without significantly impacting glycolysis.
  • The activation of OxPhos is linked to the Akt pathway, which is triggered by these factors and promotes mitochondrial function, revealing important insights into how different cell types undergo bone formation.

Article Abstract

Osteogenic differentiation, the process by which bone marrow mesenchymal stem/stromal (a.k.a. skeletal stem) cells and osteoprogenitors form osteoblasts, is a critical event for bone formation during development, fracture repair, and tissue maintenance. Extra cellular and intracellular signaling pathways triggering osteogenic differentiation are relatively well known; however, the ensuing change in cell energy metabolism is less clearly defined. We and others have previously reported activation of mitochondria during osteogenic differentiation. To further elucidate the involved bioenergetic mechanisms and triggers, we tested the effect of osteogenic media containing ascorbate and β-glycerol phosphate, or various osteogenic hormones and growth factors on energy metabolism in long bone (ST2)- and calvarial bone (MC3T3-E1)-derived osteoprogenitors. We show that osteogenic media and differentiation factors, Wnt3a and BMP2, stimulate mitochondrial oxidative phosphorylation (OxPhos) with little effect on glycolysis. The activation of OxPhos occurs acutely, suggesting a metabolic signaling change rather than protein expression change. To this end, we found that the observed mitochondrial activation is Akt dependent. Akt is activated by osteogenic media, Wnt3a, and BMP2, leading to increased phosphorylation of various mitochondrial Akt targets, a phenomenon known to stimulate OxPhos. In sum, our data provide comprehensive analysis of cellular bioenergetics during osteoinduction in cells of two different origins (mesenchyme vs neural crest) and identify Wnt3a and BMP2 as physiological stimulators of mitochondrial respiration through Akt activation.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876359PMC
http://dx.doi.org/10.1089/scd.2020.0141DOI Listing

Publication Analysis

Top Keywords

osteogenic differentiation
16
energy metabolism
12
osteogenic media
12
wnt3a bmp2
12
osteogenic
8
differentiation
5
akt
5
metabolism osteogenic
4
differentiation role
4
role akt
4

Similar Publications

Simple Preparation and Bone Regeneration Effects of Poly(vinyl alcohol)-Resveratrol Self-Cross-Linked Hydrogels.

ACS Omega

December 2024

Department of Radiotherapy Oncology, Changzhou No.2 People's Hospital, Nanjing Medical University, Changzhou 213003, China.

Hydrogels have broad application prospects in bone repair. Pure poly(vinyl alcohol) (PVA) hydrogels have limited applications because of their low hardness and poor mechanical properties. This study found that resveratrol (Res) and PVA self-assembled and cross-linked through the formation of strong hydrogen bonds after freeze-thawing, forming an easily available PVA-Res supramolecular hydrogel through a green process.

View Article and Find Full Text PDF

Immunomodulation has emerged as a promising strategy for promoting bone regeneration. However, designing osteoimmunomodulatory biomaterial that can respond to mechanical stress in the unique microenvironment of alveolar bone under continuous occlusal stress remains a significant challenge. Herein, a wireless piezoelectric stimulation system, namely, piezoelectric hydrogel incorporating BaTiO nanoparticles (BTO NPs), is successfully developed to generate piezoelectric potentials for modulating macrophage reprogramming.

View Article and Find Full Text PDF

Skeletal disorders pose significant challenges to health and quality of life, underscoring the critical need for innovative bone repair methods. Recent studies have spotlighted the promising role of extracellular vesicles (EVs) derived from bone marrow mesenchymal stem cells (BMSCs) in conjunction with biomimetic peptide (BP) WKYMVm (WK) for bone repair. This research leveraged a self-healing hydrogel as a carrier, effectively loading EVs and WK to enhance treatment efficacy.

View Article and Find Full Text PDF

Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) can be isolated from umbilical cords which is abundant and easy to obtain. Due to their potent immunosuppressive properties, multilineage differentiation potential, and lack of ethical issues, WJ-MSCs are considered a promising candidate for therapeutic applications. However, large-scale in vitro expansion is necessary to obtain enough cells for therapeutic purposes.

View Article and Find Full Text PDF

380 MPa-30% grade biodegradable Zn-Mn-Mg-Ca alloy: Bimodal grain structure, large work-hardening strain, and enhanced biocompatibility.

Acta Biomater

December 2024

Beijing Advanced Innovation Center for Materials Genome Engineering, State Key Laboratory for Advanced Metals and Materials, School of Materials Science and Engineering, University of Science and Technology Beijing, Beijing 100083, PR China; Institute of Materials Intelligent Technology, Liaoning Academy of Materials, Shenyang 110004, China. Electronic address:

Strain softening is a common issue for high-strength biodegradable Zn alloys. We developed Zn-0.6Mn-0.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!