miR-126 regulates platelet-derived growth factor receptor-α expression and migration of primary human osteoblasts

2015 ◽  
Vol 396 (1) ◽  
pp. 61-70 ◽  
Author(s):  
Yvonne Schmidt ◽  
Filip Simunovic ◽  
Sandra Strassburg ◽  
Dietmar Pfeifer ◽  
G. Björn Stark ◽  
...  
Keyword(s):  
Growth Factor ◽  
Bone Development ◽  
Growth Factor Receptor ◽  
Cell Types ◽  
Negative Regulator ◽  
Platelet Derived Growth Factor ◽  
Loss Of Function ◽  
Human Osteoblasts ◽  
Primary Human Osteoblasts ◽  
And Migration

Abstract Adequate vascularization is an essential requirement for bone development, fracture healing and bone tissue engineering. We have previously described the coculture of primary human osteoblasts (hOBs) and human endothelial cells (HUVECs), designed to investigate the interactions between these cells. In this system, we showed that cocultivation of these two cell types leads to a downregulation of platelet-derived growth factor receptor-α (PDGFR-α) in hOBs, which was a consequence of reduced mRNA stability. In the current study we investigated the possible involvement of microRNAs in this process. Firstly, we performed a microarray analysis of osteoblastic miRNAs following cocultivation with HUVECs, revealing an upregulation of miR-126. This result was confirmed by RT-qPCR, and we observed that the increase is dependent on direct cell-to-cell contacts. Gain-of-function and loss-of-function experiments showed that miR-126 is a negative regulator of PDGFR-α mRNA. Additionally, migration of hOBs was inhibited by miR-126 overexpression and stimulated by miR-126 inhibition. Addition of PDGFR-α blocking antibody to hOB culture also inhibited hOB migration. There was no effect of miR-126 modulation on osteoblast proliferation, apoptosis rate or differentiation. In conclusion, we report that the miR-126/PDGFR-α system regulates the migratory behavior of human osteoblasts, without exerting effects on cell survival and differentiation.

Two functionally distinct pools of Src kinases for PDGF receptor signalling

2005 ◽  
Vol 33 (6) ◽  
pp. 1313-1315 ◽  
Author(s):  
L. Veracini ◽  
M. Franco ◽  
A. Boureux ◽  
V. Simon ◽  
S. Roche ◽  
...  
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Tyrosine Kinases ◽  
Growth Factor Receptor ◽  
Platelet Derived Growth Factor ◽  
Pdgf Receptor ◽  
Actin Assembly ◽  
Cell Responses ◽  
Receptor Signalling ◽  
And Migration

The cytoplasmic tyrosine kinases of the Src family (SFK) play important roles in cell responses induced by growth factors, including cell growth, survival and migration. Here, we review how SFK participate in PDGF (platelet-derived growth factor) receptor signalling leading to DNA synthesis and actin assembly. Furthermore, evidence for a spatial compartmentalization of SFK signalling is also discussed.

scholarly journals Postnatal Tendon Growth and Remodeling Requires Platelet-Derived Growth Factor Receptor Signaling

2017 ◽  
Author(s):  
Kristoffer B Sugg ◽  
James F Markworth ◽  
Nathaniel P Disser ◽  
Andrew M Rizzi ◽  
Jeffrey R Talarek ◽  
...  
Keyword(s):  
Growth Factor ◽  
Biological Activities ◽  
Growth Factor Receptor ◽  
Normal Growth ◽  
Platelet Derived Growth Factor ◽  
Growth And Remodeling ◽  
Fibroblast Migration ◽  
Membrane Type ◽  
And Migration

ABSTRACTPlatelet-derived growth factor receptor (PDGFR) signaling plays an important role in the fundamental biological activities of many cells that compose musculoskeletal tissues. However, little is known about the role of PDGFR signaling during tendon growth and remodeling in adult animals. Using the hindlimb synergist ablation model of tendon growth, our objectives were to determine the role of PDGFR signaling in the adaptation of tendons subjected to a mechanical growth stimulus, as well as to investigate the biological mechanisms behind this response. We demonstrate that both PDGFRs, PDGFRα and PDGFRβ, are expressed in tendon fibroblasts, and that the inhibition of PDGFR signaling suppresses the normal growth of tendon tissue in response to mechanical growth cues due to defects in fibroblast proliferation and migration. We also identify that membrane type-1 matrix metalloproteinase (MT1-MMP) as an essential proteinase for the migration of tendon fibroblasts through their extracellular matrix. Furthermore, we report that MT1-MMP translation is regulated by PI3K/Akt signaling, while ERK1/2 controls post-translational trafficking of MT1-MMP to the plasma membrane of tendon fibroblasts. Taken together, these findings demonstrate that PDGFR signaling is necessary for postnatal tendon growth and remodeling, and that MT1-MMP is a critical mediator of tendon fibroblast migration and a potential target for the treatment of tendon injuries and diseases.

scholarly journals NHERF Links the N-Cadherin/Catenin Complex to the Platelet-derived Growth Factor Receptor to Modulate the Actin Cytoskeleton and Regulate Cell Motility

2007 ◽  
Vol 18 (4) ◽  
pp. 1220-1232 ◽  
Author(s):  
Christopher S. Theisen ◽  
James K. Wahl ◽  
Keith R. Johnson ◽  
Margaret J. Wheelock
Keyword(s):  
Cell Migration ◽  
Growth Factor ◽  
Kinase Inhibitor ◽  
Pdz Domain ◽  
Growth Factor Receptor ◽  
Cell Types ◽  
Platelet Derived Growth Factor ◽  
Binding Motif ◽  
Pdz Domains ◽  
Dependent Cell

Using phage display, we identified Na+/H+ exchanger regulatory factor (NHERF)-2 as a novel binding partner for the cadherin-associated protein, β-catenin. We showed that the second of two PSD-95/Dlg/ZO-1 (PDZ) domains of NHERF interacts with a PDZ-binding motif at the very carboxy terminus of β-catenin. N-cadherin expression has been shown to induce motility in a number of cell types. The first PDZ domain of NHERF is known to bind platelet-derived growth factor-receptor β (PDGF-Rβ), and the interaction of PDGF-Rβ with NHERF leads to enhanced cell spreading and motility. Here we show that β-catenin and N-cadherin are in a complex with NHERF and PDGF-Rβ at membrane ruffles in the highly invasive fibrosarcoma cell line HT1080. Using a stable short hairpin RNA system, we showed that HT1080 cells knocked down for either N-cadherin or NHERF had impaired ability to migrate into the wounded area in a scratch assay, similar to cells treated with a PDGF-R kinase inhibitor. Cells expressing a mutant NHERF that is unable to associate with β-catenin had increased stress fibers, reduced lamellipodia, and impaired cell migration. Using HeLa cells, which express little to no PDGF-R, we introduced PDGF-Rβ and showed that it coimmunoprecipitates with N-cadherin and that PDGF-dependent cell migration was reduced in these cells when we knocked-down expression of N-cadherin or NHERF. These studies implicate N-cadherin and β-catenin in cell migration via PDGF-R–mediated signaling through the scaffolding molecule NHERF.

scholarly journals Postnatal tendon growth and remodeling require platelet-derived growth factor receptor signaling

2018 ◽  
Vol 314 (4) ◽  
pp. C389-C403 ◽  
Author(s):  
Kristoffer B. Sugg ◽  
James F. Markworth ◽  
Nathaniel P. Disser ◽  
Andrew M. Rizzi ◽  
Jeffrey R. Talarek ◽  
...  
Keyword(s):  
Growth Factor ◽  
Biological Activities ◽  
Growth Factor Receptor ◽  
Normal Growth ◽  
Platelet Derived Growth Factor ◽  
Growth And Remodeling ◽  
Fibroblast Migration ◽  
And Migration ◽  
Phosphoinositide 3 Kinase

Platelet-derived growth factor receptor (PDGFR) signaling plays an important role in the fundamental biological activities of many cells that compose musculoskeletal tissues. However, little is known about the role of PDGFR signaling during tendon growth and remodeling in adult animals. Using the hindlimb synergist ablation model of tendon growth, our objectives were to determine the role of PDGFR signaling in the adaptation of tendons subjected to a mechanical growth stimulus, as well as to investigate the biological mechanisms behind this response. We demonstrate that both PDGFRs, PDGFRα and PDGFRβ, are expressed in tendon fibroblasts and that the inhibition of PDGFR signaling suppresses the normal growth of tendon tissue in response to mechanical growth cues due to defects in fibroblast proliferation and migration. We also identify membrane type-1 matrix metalloproteinase (MT1-MMP) as an essential proteinase for the migration of tendon fibroblasts through their extracellular matrix. Furthermore, we report that MT1-MMP translation is regulated by phosphoinositide 3-kinase/Akt signaling, while ERK1/2 controls posttranslational trafficking of MT1-MMP to the plasma membrane of tendon fibroblasts. Taken together, these findings demonstrate that PDGFR signaling is necessary for postnatal tendon growth and remodeling and that MT1-MMP is a critical mediator of tendon fibroblast migration and a potential target for the treatment of tendon injuries and diseases.

scholarly journals Platelet-Derived Growth Factor Receptor Association with Na+/H+ Exchanger Regulatory Factor Potentiates Receptor Activity

2000 ◽  
Vol 20 (22) ◽  
pp. 8352-8363 ◽  
Author(s):  
Stuart Maudsley ◽  
A. Musa Zamah ◽  
Nadeem Rahman ◽  
Jeremy T. Blitzer ◽  
Louis M. Luttrell ◽  
...  
Keyword(s):  
Growth Factor ◽  
Tyrosine Kinase ◽  
Intracellular Signaling ◽  
Pdz Domain ◽  
Growth Factor Receptor ◽  
Cell Types ◽  
Platelet Derived Growth Factor ◽  
Regulatory Factor ◽  
In Cells

ABSTRACT Platelet-derived growth factor (PDGF) is a potent mitogen for many cell types. The PDGF receptor (PDGFR) is a receptor tyrosine kinase that mediates the mitogenic effects of PDGF by binding to and/or phosphorylating a variety of intracellular signaling proteins upon PDGF-induced receptor dimerization. We show here that the Na+/H+ exchanger regulatory factor (NHERF; also known as EBP50), a protein not previously known to interact with the PDGFR, binds to the PDGFR carboxyl terminus (PDGFR-CT) with high affinity via a PDZ (PSD-95/Dlg/Z0-1 homology) domain-mediated interaction and potentiates PDGFR autophosphorylation and extracellular signal-regulated kinase (ERK) activation in cells. A point-mutated version of the PDGFR, with the terminal leucine changed to alanine (L1106A), cannot bind NHERF in vitro and is markedly impaired relative to the wild-type receptor with regard to PDGF-induced autophosphorylation and activation of ERK in cells. NHERF potentiation of PDGFR signaling depends on the capacity of NHERF to oligomerize. NHERF oligomerizes in vitro when bound with PDGFR-CT, and a truncated version of the first NHERF PDZ domain that can bind PDGFR-CT but which does not oligomerize reduces PDGFR tyrosine kinase activity when transiently overexpressed in cells. PDGFR activity in cells can also be regulated in a NHERF-dependent fashion by stimulation of the β2-adrenergic receptor, a known cellular binding partner for NHERF. These findings reveal that NHERF can directly bind to the PDGFR and potentiate PDGFR activity, thus elucidating both a novel mechanism by which PDGFR activity can be regulated and a new cellular role for the PDZ domain-containing adapter protein NHERF.

scholarly journals Marker Expression of Interstitial Cells in Human Skeletal Muscle: An Immunohistochemical Study

2019 ◽  
Vol 67 (11) ◽  
pp. 825-844
Author(s):  
Eva K. Hejbøl ◽  
Mohammad A. Hajjaj ◽  
Ole Nielsen ◽  
Henrik D. Schrøder
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Growth Factor ◽  
Human Skeletal Muscle ◽  
Interstitial Cell ◽  
Growth Factor Receptor ◽  
Cell Types ◽  
Interstitial Cells ◽  
Platelet Derived Growth Factor ◽  
Myogenic Stem Cells

There is a growing recognition that myogenic stem cells are influenced by their microenvironment during regeneration. Several interstitial cell types have been described as supportive for myoblasts. In this role, both the pericyte as a possible progenitor for mesenchymal stem cells, and interstitial cells in the endomysium have been discussed. We have applied immunohistochemistry on normal and pathological human skeletal muscle using markers for pericytes, or progenitor cells and found a cell type co-expressing CD10, CD34, CD271, and platelet-derived growth factor receptor α omnipresent in the endomysium. The marker profile of these cells changed dynamically in response to muscle damage and atrophy, and they proliferated in response to damage. The cytology and expression profile of the CD10+ cells indicated a capacity to participate in myogenesis. Both morphology and indicated function of these cells matched properties of several previously described interstitial cell types. Our study suggests a limited number of cell types that could embrace many of these described cell types. Our study indicate that the CD10+, CD34+, CD271+, and platelet-derived growth factor receptor α+ cells could have a supportive role in human muscle regeneration, and thus the mechanisms by which they exert their influence could be implemented in stem cell therapy.

scholarly journals Platelet-Derived Growth Factor Receptor β-Subtype Regulates Proliferation and Migration of Gonocytes

Endocrinology ◽  
2008 ◽  
Vol 149 (12) ◽  
pp. 6226-6235 ◽  
Author(s):  
Sabrina Basciani ◽  
Gabriele De Luca ◽  
Susanna Dolci ◽  
Marina Brama ◽  
Mario Arizzi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Growth Factor ◽  
Growth Factor Receptor ◽  
Basal Membrane ◽  
Platelet Derived Growth Factor ◽  
Seminiferous Tubules ◽  
Germline Stem Cells ◽  
Time Period ◽  
And Migration ◽  
Proliferation And Migration

Proliferation and migration of gonocytes, the precursors of spermatogonial stem cells, to the germline niche in the basal membrane of the seminiferous tubules, are two crucial events that take place between postnatal d 0.5 (P0.5) and P5.0 in the mouse and involve a selection of the cells that are committed to the germline stem cells lineage. Here we show that from embryonic d 18.0 (E18) and up to P5, the gonocytes express platelet-derived growth factor (PDGF) receptor β-subtype (PDGFR-β) and that during the same time period, the Sertoli cells express PDGF-B and PDGF-D, both ligands for PDGFR-β. Inhibition of the PDGFR-β tyrosine kinase activity during the first five postnatal days provokes a profound reduction of gonocyte number through inhibition of their proliferation and induction of apoptosis. Moreover, we found that PDGFR-β ligands are chemotactic for gonocytes. These data suggest that PDGFR-β activation has the remarkable capability to drive the selection, survival, and migration of the gonocytes from the center of the seminiferous tubules to the testicular germline niche on the basal membrane.

Sign in / Sign up

Export Citation Format

Share Document