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Proinflammatory Mediators Enhance the Osteogenesis of Human Mesenchymal Stem Cells after Lineage Commitment.

ABSTRACT: Several inflammatory processes underlie excessive bone formation, including chronic inflammation of the spine, acute infections, or periarticular ossifications after trauma. This suggests that local factors in these conditions have osteogenic properties. Mesenchymal stem cells (MSCs) and their differentiated progeny contribute to bone healing by synthesizing extracellular matrix and inducing mineralization. Due to the variation in experimental designs used in vitro, there is controversy about the osteogenic potential of proinflammatory factors on MSCs. Our goal was to determine the specific conditions allowing the pro-osteogenic effects of distinct inflammatory stimuli. Human bone marrow MSCs were exposed to tumor necrosis factor alpha (TNF-?) and lipopolysaccharide (LPS). Cells were cultured in growth medium or osteogenic differentiation medium. Alternatively, bone morphogenetic protein 2 (BMP-2) was used as osteogenic supplement to simulate the conditions in vivo. Alkaline phosphatase activity and calcium deposition were indicators of osteogenicity. To elucidate lineage commitment-dependent effects, MSCs were pre-differentiated prior treatment. Our results show that TNF-? and LPS do not affect the expression of osteogenic markers by MSCs in the absence of an osteogenic supplement. In osteogenic differentiation medium or together with BMP-2 however, these mediators highly stimulated their alkaline phosphatase activity and subsequent matrix mineralization. In pre-osteoblasts, matrix mineralization was significantly increased by these mediators, but irrespective of the culture conditions. Our study shows that inflammatory factors potently enhance the osteogenic capacity of MSCs. These properties may be harnessed in bone regenerative strategies. Importantly, the commitment of MSCs to the osteogenic lineage greatly enhances their responsiveness to inflammatory signals.

SUBMITTER: Croes M

PROVIDER: S-EPMC4503569 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Proinflammatory Mediators Enhance the Osteogenesis of Human Mesenchymal Stem Cells after Lineage Commitment.

Croes Michiel M Oner F Cumhur FC Kruyt Moyo C MC Blokhuis Taco J TJ Bastian Okan O Dhert Wouter J A WJ Alblas Jacqueline J

PloS one 20150715 7

Several inflammatory processes underlie excessive bone formation, including chronic inflammation of the spine, acute infections, or periarticular ossifications after trauma. This suggests that local factors in these conditions have osteogenic properties. Mesenchymal stem cells (MSCs) and their differentiated progeny contribute to bone healing by synthesizing extracellular matrix and inducing mineralization. Due to the variation in experimental designs used in vitro, there is controversy about th ...[more]

PMID: 26176237

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Project description:Development and maintenance of a vascular network are critical for bone growth and homeostasis; strategies that promote vascular function are critical for clinical success of tissue-engineered bone constructs. Co-culture of endothelial cells (ECs) with mesenchymal stem cells (MSCs) and exposure to 10% cyclic tensile strain have both been shown to regulate osteogenesis in isolation, but potential synergistic effects have yet to be explored. The objective of this study was to expose an MSC-EC co-culture to 10% cyclic tensile strain to examine the role of this mechanical stimulus on MSC-EC behavior. We hypothesized that paracrine signaling from ECs would stimulate osteogenesis of MSCs, and exposure to 10% cyclic tensile strain would enhance this anabolic signal. Human umbilical vein ECs and human bone marrow-derived MSCs were either monocultured or co-cultured at a 1:1 ratio in a mixed osteo/angiogenic medium, exposed to 10% cyclic tensile strain at 1?Hz for 4?h/day for 2 weeks, and biochemically and histologically analyzed for endothelial and osteogenic markers. While neither 10% cyclic tensile strain nor co-culture alone had a significant effect on osteogenesis, the concurrent application of strain to an MSC-EC co-culture resulted in a significant increase in calcium accretion and mineral deposition, suggesting that co-culture and strain synergistically enhance osteogenesis. Neither co-culture, 10% cyclic tensile strain, nor a combination of these stimuli affected endothelial markers, indicating that the endothelial phenotype remained stable, but unresponsive to the stimuli evaluated in this study. This study is the first to investigate the role of cyclic tensile strain on the complex interplay between ECs and MSCs in co-culture. The results of this study provide key insights into the synergistic effects of 10% cyclic tensile strain and co-culture on osteogenesis. Understanding mechanobiological factors affecting MSC-EC crosstalk will help enhance strategies for creating vascularized tissues in tissue engineering and regenerative medicine.

Dataset Information

Proinflammatory Mediators Enhance the Osteogenesis of Human Mesenchymal Stem Cells after Lineage Commitment.

Publications

Proinflammatory Mediators Enhance the Osteogenesis of Human Mesenchymal Stem Cells after Lineage Commitment.

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