Carbon black suppresses the osteogenesis of mesenchymal stem cells: the role of mitochondria

Abstract

BackgroundThe rapid increase in carbon black poses threats to human health. We evaluated the effect of CB (Printex 90) on the osteogenesis of bone-marrow-derived mesenchymal stem cells (MSCs). Mitochondria play an important role in the osteogenesis of MSCs and are potential targets of nanomaterials, so we studied the role of mitochondria in the CB Printex 90-induced effects on osteogenesis.ResultsLow doses of Printex 90 (3 ng/mL and 30 ng/mL) that did not cause deleterious effects on MSCs’ viability significantly inhibited osteogenesis of MSCs. Printex 90 caused down-regulation of osteoblastic markers, reduced activity of alkaline phosphatase (ALP), and poor mineralization of osteogenically induced MSCs. Cellular ATP production was decreased, mitochondrial respiration was impaired with reduced expression of ATPase, and the mitochondrial membrane was depolarized. The quantity and quality of mitochondria are tightly controlled by mitochondrial biogenesis, mitochondrial dynamics and mitophagy. The transcriptional co-activator and transcription factors for mitochondrial biogenesis, PGC-1α, Nrf1 and TFAM, were suppressed by Printex 90 treatment, suggesting that decreased biogenesis was caused by Printex 90 treatment during osteogenesis. Mitochondrial fusion and fission were significantly inhibited by Printex 90 treatment. PINK1 accumulated in Printex 90-treated cells, and more Parkin was recruited to mitochondria, indicating that mitophagy increased to remove the damaged mitochondria.ConclusionsThis is the first report of the inhibitory effects of CB on the osteogenesis of MSCs and the involvement of mitochondria in CB Printex 90-induced suppression of MSC osteogenesis.Electronic supplementary materialThe online version of this article (10.1186/s12989-018-0253-5) contains supplementary material, which is available to authorized users.

Bone Tissue Engineering via Carbon‐Based Nanomaterials

“…First, current studies mainly focus on the fabrications of carbon‐based scaffolds that could promote cell proliferation, osteogenic differentiation and bone tissue regeneration, while the mechanism behind the altered biological and mechanical effects was far less investigated . Without proper understanding of mechanism (i.e., structure‐effect relationship, etc.)…”

Mitochondrial Dynamics: Fission and Fusion in Fate Determination of Mesenchymal Stem Cells

“…Stimuli such as oxidative stress often induce single changes in mitochondrial dynamics, especially fission activation, in which a strategy unilaterally targeting mitochondrial fission can achieve desirable results with reduced risk. However, the situation is sometimes complicated, and differentiation suppression in MSCs is accompanied by both abnormal fission and fusion (Shen et al, 2018b;Marycz et al, 2019;Yao et al, 2019). In such cases, changes in mitochondrial dynamics may involve a variety of dynamic-related proteins.…”

“…These mitochondrial malfunctions were attributed to damaged mitochondrial biogenesis and mitochondrial fusion (Shen et al, 2018a). Similarly, treatment with carbon black Printex 90, a representative carbonaceous particle toxicant, induced mitochondrial dysfunction in BMSCs, which is closely related to suppressed mitochondrial biogenesis and mitochondrial dynamics, ultimately resulting in impaired osteogenic potential of BMSCs (Shen et al, 2018b).…”

Vitamin K2 Can Rescue the Dexamethasone-Induced Downregulation of Osteoblast Autophagy and Mitophagy Thereby Restoring Osteoblast Function In Vitro and In Vivo

“…The linkage of p62 to ubiquitin on the mitochondria and LC3-II (the lipidated form of LC3) on autophagosomes provides a physical attachment point for mitophagy (Geisler et al, 2010;Palikaras et al, 2018), and disruption of either PINK1 or Parkin leads to the impaired mitophagy (Han et al, 2015;Lazarou et al, 2015). Interestingly, impaired mitophagic function have been reported to negatively impact osteoblast differentiation and mineralization function in vitro (Shen et al, 2018b;Jing et al, 2020) and the restoration of mitophagy helps alleviate steriod-induced bone loss in vivo (Zhang et al, 2020). Despite these encouraging reports, the precise role of autophagy and mitophagy in osteoblastic differentiation and function has not been thoroughly explored.…”