Cyclic tensile strain and cyclic hydrostatic pressure differentially regulate expression of hypertrophic markers in primary chondrocytes

Wong, Maylene; Siegrist, Mark; Goodwin, Kelly

doi:10.1016/s8756-3282(03)00242-4

Cited by 218 publications

(169 citation statements)

References 34 publications

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“…Application of intermittent compressive force to fetal mouse calvariae was shown to increase bone formation and decrease bone resorption (Klein-Nulend et al, 1987). Indeed, application of pressure may have different effects than strain: chondrocytes subjected to cyclical tension caused increased MMP-13 and decreased TIMP-1 gene expression while cyclical hydrostatic pressure increased TIMP-1 and decreased MMP-13 (Wong et al, 2003). These results support the idea that chondrocytes can distinguish the type of mechanical force, responding appropriately to hydrostatic pressure with slowed chondrocytic differentiation and to cyclical strain with hypertrophy.…”

Section: What Mechanical Factors Are Generated By Loading?mentioning

confidence: 53%

Molecular pathways mediating mechanical signaling in bone

Rubin

Jacobs

2006

Gene

400

303

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Bone tissue has the capacity to adapt to its functional environment such that its morphology is "optimized" for the mechanical demand. The adaptive nature of the skeleton poses an interesting set of biological questions (e.g., how does bone sense mechanical signals, what cells are the sensing system, what are the mechanical signals that drive the system, what receptors are responsible for transducing the mechanical signal, what are the molecular responses to the mechanical stimuli). Studies of the characteristics of the mechanical environment at the cellular level, the forces that bone cells recognize, and the integrated cellular responses are providing new information at an accelerating speed. This review first considers the mechanical factors that are generated by loading in the skeleton, including strain, stress and pressure. Mechanosensitive cells placed to recognize these forces in the skeleton, osteoblasts, osteoclasts, osteocytes and cells of the vasculature are reviewed. The identity of the mechanoreceptor(s) is approached, with consideration of ion channels, integrins, connexins, the lipid membrane including caveolar and noncaveolar lipid rafts and the possibility that altering cell shape at the membrane or cytoskeleton alters integral signaling protein associations. The distal intracellular signaling systems on-line after the mechanoreceptor is activated are reviewed, including those emanating from G-proteins (e.g., intracellular calcium shifts), MAPKs, and nitric oxide. The ability to harness mechanical signals to improve bone health through devices and exercise is broached. Increased appreciation of the importance of the mechanical environment in regulating and determining the structural efficacy of the skeleton makes this an exciting time for further exploration of this area.

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Section: What Mechanical Factors Are Generated By Loading?mentioning

confidence: 53%

Molecular pathways mediating mechanical signaling in bone

Rubin

Jacobs

2006

Gene

400

303

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“…6 Cyclic tension significantly increased lubricin expression in primary chondrocytes, while hydrostatic pressure did not significantly alter expression. 21 Shear force in the form of surface motion upregulated lubricin expression, but axial compression alone had no effect. 22 Consistent with these findings, we found variations in lubricin expression along the FDP, corresponding to regions that differ in mechanical environment.…”

Section: Discussionmentioning

confidence: 99%

“…Cyclic tension significantly increases lubricin expression in primary chondrocytes. 21 Surface motion but not compression was found to upregulate lubricin expression in chondrocyteseeded three-dimensional scaffolds. 22 The flexor digitorum profundus (FDP) is one of the longest and most complicated tendons in the human body.…”

Section: Introductionmentioning

confidence: 95%

Expression and mapping of lubricin in canine flexor tendon

et al. 2006

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Matrix composition and the biomechanical environment are intimately interdependent in most connective tissues. Lubricin has many distinct biological functions, including lubrication, antiadhesion, and cytoprotection in cartilage, tendons, and other tissues. This study investigated the distribution of lubricin in the canine flexor digitorum profundus (FDP) tendon by immunohistochemistry. Lubricin was found both on the tendon surface and at the interface of collagen fiber bundles within the tendon, where the cells are subjected to shear force in addition to tension and compression. The expression of lubricin in regions of the canine flexor tendon that differ in mechanical or nutritional environment was also investigated using RT-PCR. Six N-terminal splicing variants were identified from six distinct anatomical regions of flexor tendon. The variants with larger sizes were noted in regions subjected to significant shear and compressive forces. Lubricin is ubiquitous in the FDP tendon, with variations in distribution and splicing that appear to correspond to discrete anatomic locations that differ by mechanical or nutritional environment. ß

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“…The response of those cells was studied under cyclic hydrostatic pressure and tension, respectively (Lucchinetti et al, 2004;Fan et al, 2009). This discrepancy is likely due to not only their differentiated stage but also the different biomechanical loading regimes, since a strain specifi c regulation seems to be more the rule (Wong et al, 2003). This is especially important, since most former expression analyses of CD29 in mesenchymal cells were not conducted using compression.…”

Section: Mechanoregulation Of Cd73 and Cd29 In Mscsmentioning

confidence: 99%

CD73 and CD29 concurrently mediate the mechanically induced decrease of migratory capacity of mesenchymal stromal cells

Ode

Kopf²,

Kurtz³

et al. 2011

eCM

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The assumption that mesenchymal stromal cell (MSC)-based-therapies are capable of augmenting physiological regeneration processes has fostered intensive basic and clinical research activities. However, to achieve sustained therapeutic success in vivo, not only the biological, but also the mechanical microenvironment of MSCs during these regeneration processes needs to be taken into account. This is especially important for e.g., bone fracture repair, since MSCs present at the fracture site undergo signifi cant biomechanical stimulation. This study has therefore investigated cellular characteristics and the functional behaviour of MSCs in response to mechanical loading.Our results demonstrated a reduced expression of MSC surface markers CD73 (ecto-5'-nucleotidase) and CD29 (integrin β1) after loading. On the functional level, loading led to a reduced migration of MSCs. Both effects persisted for a week after the removal of the loading stimulus. Specifi c inhibition of CD73/CD29 demonstrated their substrate dependent involvement in MSC migration after loading. These results were supported by scanning electron microscopy images and phalloidin staining of actin fi laments displaying less cell spreading, lamellipodia formation and actin accumulations. Moreover, focal adhesion kinase and Src-family kinases were identifi ed as candidate downstream targets of CD73/CD29 that might contribute to the mechanically induced decrease in MSC migration.These results suggest that MSC migration is controlled by CD73/CD29, which in turn are regulated by mechanical stimulation of cells. We therefore speculate that MSCs migrate into the fracture site, become mechanically entrapped, and thereby accumulate to fulfi l their regenerative functions.

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Cyclic tensile strain and cyclic hydrostatic pressure differentially regulate expression of hypertrophic markers in primary chondrocytes

Cited by 218 publications

References 34 publications

Molecular pathways mediating mechanical signaling in bone

Molecular pathways mediating mechanical signaling in bone

Expression and mapping of lubricin in canine flexor tendon

CD73 and CD29 concurrently mediate the mechanically induced decrease of migratory capacity of mesenchymal stromal cells

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