Musculoskeletal mechanobiology: Interpretation by external force and engineered substratum

McCullen, Seth D.; Haslauer, Carla M.; Loboa, Elizabeth G.

doi:10.1016/j.jbiomech.2009.09.017

Cited by 26 publications

(29 citation statements)

References 74 publications

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“…For chondrocytes, mechanotransduction results in quantitative modulation of the rates of ECM synthesis and degradation, thus enabling them to alter the composition of the cartilage matrix [4]. While mechanotransduction pathways of mature skeletal tissues have been studied in great detail [5], our knowledge is considerably limited regarding how mechanical forces (e.g. embryonic or foetal movements) affect developing cartilage and cellular differentiation in general.…”

Section: Introductionmentioning

confidence: 99%

Mechanical loading stimulates chondrogenesis via the PKA/CREB-Sox9 and PP2A pathways in chicken micromass cultures

Juhász

Matta

Somogyi

et al. 2014

Cellular Signalling

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Biomechanical stimuli play important roles in the formation of articular cartilage during early foetal life, and optimal mechanical load is a crucial regulatory factor of adult chondrocyte metabolism and function. In this study, we undertook to analyse mechanotransduction pathways during in vitro chondrogenesis. Chondroprogenitor cells isolated from limb buds of 4-day-old chicken embryos were cultivated as high density cell cultures for 6 days. Mechanical stimulation was carried out by a self-designed bioreactor that exerted uniaxial intermittent cyclic load transmitted by the culture medium as hydrostatic pressure and fluid shear to differentiating cells. The loading scheme (0.05 Hz, 600 Pa; for 30 min) was applied on culturing days 2 and 3, when final commitment and differentiation of chondroprogenitor cells occurred in this model. The applied mechanical load significantly augmented cartilage matrix production and elevated mRNA expression of several cartilage matrix constituents, including collagen type II and aggrecan core protein, as well as matrixproducing hyaluronan synthases through enhanced expression, phosphorylation and nuclear signals of the main chondrogenic transcription factor Sox9. Along with increased cAMP levels, a significantly enhanced protein kinase A (PKA) activity was also detected and CREB, the archetypal downstream transcription factor of PKA signalling, exhibited elevated phosphorylation levels and stronger nuclear signals in response to mechanical stimuli. All the above effects were diminished by the PKA-inhibitor H89. Inhibition of the PKA-independent cAMP-mediators Epac1 and Epac2 with HJC0197 resulted in enhanced cartilage formation, which was additive to that of the mechanical stimulation, implying that the chondrogenesispromoting effect of mechanical load was independent of Epac. At the same time, PP2A activity was reduced following mechanical load and treatments with the PP2A-inhibitor okadaic acid were able to mimic the effects of the intervention. Our results indicate that proper mechanical stimuli augment in vitro cartilage formation via promoting both Juhász and Matta et al. 3 differentiation and matrix production of chondrogenic cells, and the opposing regulation of the PKA/CREB-Sox9 and the PP2A signalling pathways is crucial in this phenomenon.

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Section: Introductionmentioning

confidence: 99%

Mechanical loading stimulates chondrogenesis via the PKA/CREB-Sox9 and PP2A pathways in chicken micromass cultures

Juhász

Matta

Somogyi

et al. 2014

Cellular Signalling

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“…More reports in literature are finding significant roles for the cytoskeleton in differentiation of stem cells (Engler et al 2006;McBeath et al 2004). Complicating interpretation of cytoskeletal changes is the fact that, in addition to transmitting signals from the extracellular environment, the cytoskeleton and associated factors are also tools the cell uses to react to its environment (McCullen et al 2010a). For instance, an increase in actin stress fiber formation and assembly is a typical reaction to application of tensile strain (Jaalouk and Lammerding, 2009) or increased matrix stiffness (Wells and Discher 2008).…”

Section: Hypotheses Of Mechanismmentioning

confidence: 99%

“…Calcium ions have been shown to stimulate proliferation of osteoblasts, and magnesium ions have been associated with increased mineralization (Liu et al 2008). McCullen and colleagues also showed ionic calcium enhanced mineralization by human ASCs (McCullen et al 2010a).…”

Section: Indirect and Chemical Mechanisms: Receptors Ion Channels Gmentioning

confidence: 99%

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Review of biophysical factors affecting osteogenic differentiation of human adult adipose-derived stem cells

Salazar

Onodera

2012

Biophys Rev

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Developing bone is subject to the control of a broad variety of influences in vivo. For bone repair applications, in vitro osteogenic assays are routinely used to test the responses of bone-forming cells to drugs, hormones, and biomaterials. Results of these assays are used to predict the behavior of bone-forming cells in vivo. Stem cell research has shown promise for enhancing bone repair. In vitro osteogenic assays to test the bone-forming response of stem cells typically use chemical solutions. Stem cell in vitro osteogenic assays often neglect important biophysical cues, such as the forces associated with regular weight-bearing exercise, which promote bone formation. Incorporating more biophysical cues that promote bone formation would improve in vitro osteogenic assays for stem cells. Improved in vitro osteogenic stimulation opens opportunities for "preconditioning" cells to differentiate towards the desired lineage. In this review, we explore the role of select biophysical factors-growth surfaces, tensile strain, fluid flow and electromagnetic stimulation-in promoting osteogenic differentiation of stem cells from human adipose. Emphasis is placed on the potential for physical microenvironment manipulation to translate tissue engineering and stem cell research into widespread clinical usage.

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“…In particular in the regeneration of musculoskeletal tissues, like cartilage and bone, supported loads provide cues for the right gene expression and synthesis of ECM (Huang et al, 2010b;Kelly and Jacobs, 2010;McCullen et al, 2010;Riehl et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Fatigue prediction in fibrin poly-ε-caprolactone macroporous scaffolds

Panadero

Vikingsson

Ribelles

et al. 2013

Journal of the Mechanical Behavior of Biomedical Materials

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Tissue engineering applications rely on scaffolds that during its service life, either for in-vivo or in vitro applications, are under mechanical solicitations. The variation of the mechanical condition of the scaffold is strongly relevant for cell culture and has been scarcely addressed.Fatigue life cycle of poly-ε-caprolactone, PCL, scaffolds with and without fibrin as filler of the pore structure were characterized both dry and immersed in liquid water. It is observed that the there is a strong increase from 100 to 500 in the number of loading cycles before collapse in the samples tested in immersed conditions due to the more uniform stress distributions within the samples, the fibrin loading playing a minor role in the mechanical performance of the scaffolds.

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Musculoskeletal mechanobiology: Interpretation by external force and engineered substratum

Cited by 26 publications

References 74 publications

Mechanical loading stimulates chondrogenesis via the PKA/CREB-Sox9 and PP2A pathways in chicken micromass cultures

Mechanical loading stimulates chondrogenesis via the PKA/CREB-Sox9 and PP2A pathways in chicken micromass cultures

Review of biophysical factors affecting osteogenic differentiation of human adult adipose-derived stem cells

Fatigue prediction in fibrin poly-ε-caprolactone macroporous scaffolds

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