Mechanical signals promote osteogenic fate through a primary cilia‐mediated mechanism

Chen, Julia C.; Hoey, David A.; Chua, Mardonn; Bellon, Raymond B.; Jacobs, Christopher R.

doi:10.1096/fj.15-276402

Cited by 80 publications

(67 citation statements)

References 39 publications

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“…86 Moreover, primary cilia have important roles in mechanoregulation in adult tissues by engaging the cytoskeleton to activate signalling pathways that promote the differentiation of stem cells in response to mechanical cues. 87,92 …”

Section: Stem Cells Respond To Forcesmentioning

confidence: 99%

Mechanical forces direct stem cell behaviour in development and regeneration

Vining

Mooney

2017

Nat Rev Mol Cell Biol

1,228

958

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Stem cells and their local microenvironment, or niche, communicate through mechanical, cues to regulate cell fate and cell behaviour, and to guide developmental processes. During embryonic development, mechanical forces are involved in patterning and organogenesis. The physical environment of pluripotent stem cells regulates their differentiation and self-renewal. Mechanical and physical cues are also important in adult tissues, where adult stem cells require physical interactions with the extracellular matrix to maintain their potency. In vitro, synthetic models of the stem cell niche can be used to precisely control and manipulate the biophysical and biochemical properties of the stem cell microenvironment and examine how the mode and magnitude of mechanical cues, such as matrix stiffness or applied forces, direct stem cell differentiation and function. Fundamental insights on the mechanobiology of stem cells also inform the design of artificial niches to support stem cells for regenerative therapies.

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Section: Stem Cells Respond To Forcesmentioning

confidence: 99%

Mechanical forces direct stem cell behaviour in development and regeneration

Vining

Mooney

2017

Nat Rev Mol Cell Biol

1,228

958

View full text Add to dashboard Cite

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“…Recently, Chen et al (2015) transplanted bone marrow cells from GFP-expressing mice into normal mice that were Rix et al 2011 Silencing IFT80 in C3H10T1/2 and bone marrow-derived stromal cells blocks cilia formation and osteoblast differentiation…”

Section: Primary Cilia/ift In Bone Mechanosensingmentioning

confidence: 99%

Primary Cilia and Intraflagellar Transport Proteins in Bone and Cartilage

Yuan

Yang

2016

J Dent Res

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Primary cilia, present on most mammalian cells, function as a sensor to sense the environment change and transduce signaling. Loss of primary cilia causes a group of human pleiotropic syndromes called Ciliopathies. Some of the ciliopathies display skeletal dysplasias, implying the important role of primary cilia in skeletal development and homeostasis. Emerging evidence has shown that loss or malfunction of primary cilia or ciliary proteins in bone and cartilage is associated with developmental and function defects. Intraflagellar transport (IFT) proteins are essential for cilia formation and/or function. In this review, we discuss the role of primary cilia and IFT proteins in the development of bone and cartilage, as well as the differentiation and mechanotransduction of mesenchymal stem cells, osteoblasts, osteocytes, and chondrocytes. We also include the role of primary cilia in tooth development and highlight the current advance of primary cilia and IFT proteins in the pathogenesis of cartilage diseases, including osteoarthritis, osteosarcoma, and chondrosarcoma.

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“…Primary cilia are essential for hedgehog (Hh) signaling transduction and regulate platelet‐derived growth factor and Wnt signaling . In addition to the chemical‐sensing role, primary cilia play an important role in mechanotransduction and function as a calcium signaling nexus . The presence of cilia on chondrocytes was first reported a half century ago .…”

Section: Introductionmentioning

confidence: 99%

IFT80 Is Required for Fracture Healing Through Controlling the Regulation of TGF-β Signaling in Chondrocyte Differentiation and Function

Liu

Alharbi

Graves

et al. 2019

Journal of Bone and Mineral Research

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Primary cilia are essential cellular organelles that are anchored at the cell surface membrane to sense and transduce signaling. Intraflagellar transport (IFT) proteins are indispensable for cilia formation and function. Although major advances in understanding the roles of these proteins in bone development have been made, the mechanisms by which IFT proteins regulate bone repair have not been identified. We investigated the role of the IFT80 protein in chondrocytes during fracture healing by creating femoral fractures in mice with conditional deletion of IFT80 in chondrocytes utilizing tamoxifen inducible Col2α1‐CreER mice. Col2α1creIFT80f/f mice had smaller fracture calluses than IFT80f/f (control) mice. The max‐width and max‐callus area were 31% and 48% smaller than those of the control mice, respectively. Col2α1creIFT80f/f mice formed low‐density/porous woven bony tissue with significantly lower ratio of bone volume, Trabecular (Tb) number and Tb thickness, and greater Tb spacing compared to control mice. IFT80 deletion significantly downregulated the expression of angiogenesis markers‐VEGF, PDGF and angiopoietin and inhibited fracture callus vascularization. Mechanistically, loss of IFT80 in chondrocytes resulted in a decrease in cilia formation and chondrocyte proliferation rate in fracture callus compared to the control mice. Meanwhile, IFT80 deletion downregulated the TGF‐β signaling pathway by inhibiting the expression of TGF‐βI, TGF‐βR, and phosphorylation of Smad2/3 in the fracture callus. In primary chondrocyte cultures in vitro, IFT80 deletion dramatically reduced chondrocyte proliferation, cilia assembly, and chondrogenic gene expression and differentiation. Collectively, our findings demonstrate that IFT80 and primary cilia play an essential role in fracture healing, likely through controlling chondrocyte proliferation and differentiation, and the TGF‐β signaling pathway. © 2019 American Society for Bone and Mineral Research.

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Mechanical signals promote osteogenic fate through a primary cilia‐mediated mechanism

Cited by 80 publications

References 39 publications

Mechanical forces direct stem cell behaviour in development and regeneration

Mechanical forces direct stem cell behaviour in development and regeneration

Primary Cilia and Intraflagellar Transport Proteins in Bone and Cartilage

IFT80 Is Required for Fracture Healing Through Controlling the Regulation of TGF-β Signaling in Chondrocyte Differentiation and Function

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