The Metabolic Microenvironment Steers Bone Tissue Regeneration

Loeffler, Julia; Duda, Georg N.; Sass, F. Andrea; Dienelt, Anke

doi:10.1016/j.tem.2017.11.008

Cited by 70 publications

(68 citation statements)

References 89 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Recently, there has been increased interest in the energetic profile of bone-forming cells and their progenitors. There has also been a growing interest in determining the energy metabolism of both embryonic and somatic stem cells in general as they differentiate (25). In the case of osteoblasts, these stem cells are referred to as BMSCs or skeletal stem cells (26).…”

Section: Mitochondria Promote ␤-Catenin Acetylation and Activitymentioning

confidence: 99%

Active mitochondria support osteogenic differentiation by stimulating β-catenin acetylation

Busch

White

et al. 2018

Journal of Biological Chemistry

108

View full text Add to dashboard Cite

Bone marrow stromal (a.k.a. mesenchymal stem) cells (BMSCs) can differentiate into osteoblasts (OBs), adipocytes, or chondrocytes. As BMSCs undergo OB differentiation, they up-regulate mitochondrial oxidative phosphorylation (OxPhos). Here, we investigated the mechanism(s) connecting mitochondrial OxPhos to OB differentiation. First, we found that treating BMSC-like C3H10T1/2 cells with an OxPhos inhibitor reduces their osteogenic potential. Interestingly, ATP levels were not reduced, as glycolysis compensated for the decreased OxPhos. Thus, mitochondria support OB differentiation not only by supplying ATP, but also by other mechanisms. To uncover these mechanisms, we stimulated OxPhos in C3H10T1/2 cells by replacing media glucose with galactose and observed that this substitution increases both OxPhos and osteogenesis even in the absence of osteoinducers. β-Catenin, an important signaling pathway in osteogenesis, was found to be responsive to OxPhos stimulation. β-Catenin activity is maintained by acetylation, and mitochondria generate the acetyl donor acetyl-CoA, which upon entering the Krebs cycle is converted to citrate capable of exiting mitochondria. Cytosolic citrate is converted back to acetyl-CoA by ATP citrate lyase (ACLY). We found that inhibiting ACLY with SB204990 (SB) reverses the galactose-induced β-catenin activity and OB differentiation. This suggested that acetylation is involved in β-catenin activation after forced OxPhos stimulation, and using immunoprecipitation, we indeed detected SB-sensitive β-catenin acetylation. Both β-catenin acetylation and activity increased during osteoinduction coincident with OxPhos activation. These findings suggest that active mitochondria support OB differentiation by promoting β-catenin acetylation and thus activity.

show abstract

Section: Mitochondria Promote ␤-Catenin Acetylation and Activitymentioning

confidence: 99%

Active mitochondria support osteogenic differentiation by stimulating β-catenin acetylation

Busch

White

et al. 2018

Journal of Biological Chemistry

108

View full text Add to dashboard Cite

show abstract

“…For example, after tissue injury reactions are induced at the cellular biological level, activated platelets lead to the migration of mesenchymal progenitor cells, and endothelial cells into a hypoxic environment that can modulate the cellular response. 66,67 Thus, the rate of oxygen release significantly impacts the formation of new tissues. Here, it is believed that the oxygen supply in the treated regions is largely dependent on vascularization and blood oxygenation on site, while the demand for oxygen is largely determined by the rate of cellular respiration.…”

Section: Resultsmentioning

confidence: 99%

<p>Electrospraying Oxygen-Generating Microparticles for Tissue Engineering Applications</p>

Morais¹,

Wang²,

Vieira³

et al. 2020

IJN

View full text Add to dashboard Cite

Background: The facile preparation of oxygen-generating microparticles (M) consisting of Polycaprolactone (PCL), Pluronic F-127, and calcium peroxide (CPO) (PCL-F-CPO-M) fabricated through an electrospraying process is disclosed. The biological study confirmed the positive impact from the oxygen-generating microparticles on the cell growth with high viability. The presented technology could work as a prominent tool for various tissue engineering and biomedical applications. Methods: The oxygen-generated microparticles fabricated through electrospraying processes were thoroughly characterization through various methods such as X-ray diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR) analysis, and scanning electron microscopy (SEM)/SEM-Energy Dispersive Spectroscopy (EDS) analysis. Results: The analyses confirmed the presence of the various components and the porous structure of the microparticles. Spherical shape with spongy characteristic microparticles were obtained with negative charge surface (ζ =-16.9) and a size of 17.00 ± 0.34 μm. Furthermore, the biological study performed on rat chondrocytes demonstrated good cell viability and the positive impact of increasing the amount of CPO in the PCL-F-CPO-M. Conclusion: This technological platform could work as an important tool for tissue engineering due to the ability of the microparticles to release oxygen in a sustained manner for up to 7 days with high cell viability.

show abstract

“…Among the biological processes determined by GO analysis, most of the 1,185 obtained proteins were functionally related to "cellular process," "metabolic process," "biological regulation," "regulation of biological process," "response to stimulus," and "multicellular organismal process." Cellular processes, such as cell proliferation, differentiation, and attachment, extensively participate in tissue repair [42], similar to metabolic processes [43]. Researchers compared the proteomic of human bone marrow MSCs and their exosomes under ischemic tissuesimulated conditions and found that several putative paracrine effectors of angiogenesis include platelet-derived growth factor, epidermal growth factor, fibroblast growth factor, and most notably nuclear factor kappa B (NFκB) signaling pathway proteins enriched in exosomes [44].…”

Section: Discussionmentioning

confidence: 99%

Proteomic Analysis of Exosomes from Adipose-Derived Mesenchymal Stem Cells: A Novel Therapeutic Strategy for Tissue Injury

Xing

Han

Cheng

et al. 2020

BioMed Research International

View full text Add to dashboard Cite

Exosomes are extracellular membranous nanovesicles that mediate local and systemic cell-to-cell communication by transporting functional molecules, such as proteins, into target cells, thereby affecting the behavior of receptor cells. Exosomes originating from adipose-derived mesenchymal stem cells (ADSCs) are considered a multipotent and abundant therapeutic tool for tissue injury. To investigate ADSC-secreted exosomes and their potential function in tissue repair, we isolated exosomes from the supernatants of ADSCs via ultracentrifugation, characterized them via transmission electron microscopy, nanoparticle tracking analysis, and Western blot analysis. Then, we determined their protein profile via proteomic analysis. Results showed that extracellular vesicles, which have an average diameter of 116 nm, exhibit a cup-shaped morphology and express exosomal markers. A total of 1,185 protein groups were identified in the exosomes. Gene Ontology analysis indicated that exosomal proteins are mostly derived from cells mainly involved in protein binding. Protein annotation via the Cluster of Orthologous Groups system indicated that most proteins were involved in general function prediction, posttranslational modification, protein turnover, and chaperoning. Further, pathway analysis revealed that most of the proteins obtained participated in metabolic pathways, focal adhesion, regulation of the actin cytoskeleton, and microbial metabolism. Some tissue repair-related signaling pathways were also discovered. The identified molecules might serve as potential therapeutic targets for future studies.

show abstract

The Metabolic Microenvironment Steers Bone Tissue Regeneration

Cited by 70 publications

References 89 publications

Active mitochondria support osteogenic differentiation by stimulating β-catenin acetylation

Active mitochondria support osteogenic differentiation by stimulating β-catenin acetylation

<p>Electrospraying Oxygen-Generating Microparticles for Tissue Engineering Applications</p>

Proteomic Analysis of Exosomes from Adipose-Derived Mesenchymal Stem Cells: A Novel Therapeutic Strategy for Tissue Injury

Contact Info

Product

Resources

About