TGFβ and FGF promote tendon progenitor fate and act downstream of muscle contraction to regulate tendon differentiation during chick limb development

Havis, Emmanuelle; Bonnin, Marie-Ange; Lima, Joana Esteves de; Charvet, Benjamin; Milet, Cécile; Duprez, Delphine

doi:10.1242/dev.136242

Cited by 144 publications

(162 citation statements)

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“…TGFß is a key signaling molecule for tendon development. TGFß signaling is required and sufficient for Scx/SCX expression during development in chick and mouse embryos (Pryce et al, 2009; Havis et al, 2014, 2016), while FGF signaling is required and sufficient for SCX expression in undifferentiated chick limb cells but not in mouse limb cells (Pryce et al, 2009; Havis et al, 2014, 2016). …”

Section: Connective Tissue Developmentmentioning

confidence: 99%

“…Moreover, overexpression of FGF4, which is normally expressed at the tips of muscles fibers, leads to ectopic expression of tendon-associated genes in chick limbs (Edom-Vovard et al, 2002; Eloy-trinquet et al, 2009). In addition, chick embryo immobilization decreases SCX expression in limb tendons and application of FGF4 or TGFβ ligands prevents SCX down-regulation consecutive to immobilization, demonstrating that FGF and TGFβ act downstream of mechanical forces to regulate tendon differentiation (Havis et al, 2016). …”

Section: Connective Tissue Developmentmentioning

confidence: 99%

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Non-myogenic Contribution to Muscle Development and Homeostasis: The Role of Connective Tissues

Nassari

Duprez

Fournier-Thibault

2017

Front. Cell Dev. Biol.

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Skeletal muscles belong to the musculoskeletal system, which is composed of bone, tendon, ligament and irregular connective tissue, and closely associated with motor nerves and blood vessels. The intrinsic molecular signals regulating myogenesis have been extensively investigated. However, muscle development, homeostasis and regeneration require interactions with surrounding tissues and the cellular and molecular aspects of this dialogue have not been completely elucidated. During development and adult life, myogenic cells are closely associated with the different types of connective tissue. Connective tissues are defined as specialized (bone and cartilage), dense regular (tendon and ligament) and dense irregular connective tissue. The role of connective tissue in muscle morphogenesis has been investigated, thanks to the identification of transcription factors that characterize the different types of connective tissues. Here, we review the development of the various connective tissues in the context of the musculoskeletal system and highlight their important role in delivering information necessary for correct muscle morphogenesis, from the early step of myoblast differentiation to the late stage of muscle maturation. Interactions between muscle and connective tissue are also critical in the adult during muscle regeneration, as impairment of the regenerative potential after injury or in neuromuscular diseases results in the progressive replacement of the muscle mass by fibrotic tissue. We conclude that bi-directional communication between muscle and connective tissue is critical for a correct assembly of the musculoskeletal system during development as well as to maintain its homeostasis in the adult.

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Section: Connective Tissue Developmentmentioning

confidence: 99%

Section: Connective Tissue Developmentmentioning

confidence: 99%

Non-myogenic Contribution to Muscle Development and Homeostasis: The Role of Connective Tissues

Nassari

Duprez

Fournier-Thibault

2017

Front. Cell Dev. Biol.

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“…63 These include transcription factors such as Scx and signaling pathways, including TGF-β and FGF. 71, 72 …”

Section: The Role Of Mechanical Forces In Musculoskeletal Developmentmentioning

confidence: 99%

“…While it is clear from whole-organism studies that mechanical loading is necessary for some aspects of musculoskeletal morphogenesis, specific mechanotransduction pathways can be difficult to test in vivo , although there is evidence that disruption of known pathways results in arrest or abnormal development. 59, 72, 73 In general, detailed understanding of mechanobiology pathways relies heavily on in vitro culture systems that allow for direct perturbations and measurements of forces on the cellular level. We therefore discuss three mechanisms that may potentially regulate the transduction of mechanical signals to cells in the embryo: (1) cell–extracellular matrix (ECM) transduction, (2) cell–cell interactions, and (3) primary cilium sensing.…”

Section: Molecular Regulators Of Mechanobiology In Developmentmentioning

confidence: 99%

Mechanobiology of limb musculoskeletal development

Arvind

Huang

2017

Annals of the New York Academy of Sciences

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While there has been considerable progress in identifying molecular regulators of musculoskeletal development, the role of physical forces in regulating induction, differentiation, and patterning events is less well understood. Here, we highlight recent findings in this area, focusing primarily on model systems that test the mechanical regulation of skeletal and tendon development in the limb. We also discuss a few of the key signaling pathways and mechanisms that have been implicated in mechanotransduction and highlight current gaps in knowledge and opportunities for further research in the field.

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“…IGF-1 and TGF-β are both present within the tendon matrix 18 , and in vitro have been shown to be involved in tendon cell growth, collagen production and matrix remodelling [19][20][21][22][23][24][25] . Developmental studies suggest a key role for TGFβ1 in tendon development 33 , and inhibiting TGFβ1 has generally resulted in poor healing outcomes in in vivo tendon defect models 34 . Gene expression studies, however, suggest TGFβ1 treatment may favour a chondrocytic response over a tenogenic one 22,25,35 , with our results suggesting similar movement away from a tenogenic lineage.…”

Section: Discussionmentioning

confidence: 99%

Lactoferrin and parathyroid hormone are not harmful to primary tenocytes in vitro, but PDGF may be

Musson

Tay

Chhana

et al. 2017

MLTJ

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SummaryIntroduction: Recently, bone-active factors such as parathyroid hormone and lactoferrin, have been used in pre-clinical models to promote tendon healing. How-ever, there is limited understanding of how these boneactive factors may affect the cells of the ten-don themselves. Here, we present an in vitro study assessing the effects of parathyroid hor-mone and lactoferrin on primary tendon cells (tenocytes), and compare their responses to the tenogenic factors, PDGF, IGF-1 and TGF-β. Materials and Methods: Tenocyte proliferation and collagen production were assessed by alamarBlue® and Sirius red as-says, respectively. To assess tenocyte trans-differentiation, changes in the expression of genes important in tenocyte, chondrocyte and osteoblast biology were determined using real-time PCR. Results: Parathyroid hormone and lactoferrin had no effect on tenocyte growth or collagen production, with minimal changes in gene expression and no detrimental effects observed to suggest trans-differentiation away from tendon cell behaviour. Tenogenic factors PDGF, IGF-1 and TGF all increasetenocyte collagen production, however, the gene expression data suggests that PDGF promotes severe de-differentiation of the tenocytes. Discussion: Our findings suggest that using parathyroid hormone or lactoferrin as a singular factor to promote tendon healing may not be of benefit, but for use in tendon-bone healing there would be no detrimental effect on the tendon itself.

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TGFβ and FGF promote tendon progenitor fate and act downstream of muscle contraction to regulate tendon differentiation during chick limb development

Cited by 144 publications

References 66 publications

Non-myogenic Contribution to Muscle Development and Homeostasis: The Role of Connective Tissues

Non-myogenic Contribution to Muscle Development and Homeostasis: The Role of Connective Tissues

Mechanobiology of limb musculoskeletal development

Lactoferrin and parathyroid hormone are not harmful to primary tenocytes in vitro, but PDGF may be

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