CCN1 expression is regulated by mechanical stimuli in tendons

Leong, Natalie L.; Greskovich, Kathryn E.; Blommer, Joseph; Jiang, Jie

doi:10.1016/j.bbrc.2023.04.058

Cited by 1 publication

(1 citation statement)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Corroborating the impaired molecular signals downstream of YAP, our data indicate that mechanical stress activates the expression of CYR61 and CTGF genes only in control cells. Since CYR61 has been described as an effector of mechanical cues in tendon cells exposed to cyclic-uniaxial stretching, as well as in loaded tendons with large load-bearing capacities, such as Achilles and patellar tendons [ 60 ], we can infer that the reduction in YAP activity might have a substantial impact on the physiology of the affected tendons. In the attempt to explore whether there is any relationship between the impaired ciliogenesis and the altered activation of FAs displayed by UCMD cells, we came across some studies indicating that ciliogenesis is promoted by depolymerized actin and inactive YAP [ 61 , 62 ].…”

Section: Discussionmentioning

confidence: 99%

Collagen VI Deficiency Impairs Tendon Fibroblasts Mechanoresponse in Ullrich Congenital Muscular Dystrophy

Cenni,

Sabatelli,

Di Martino

et al. 2024

Cells

View full text Add to dashboard Cite

The pericellular matrix (PCM) is a specialized extracellular matrix that surrounds cells. Interactions with the PCM enable the cells to sense and respond to mechanical signals, triggering a proper adaptive response. Collagen VI is a component of muscle and tendon PCM. Mutations in collagen VI genes cause a distinctive group of inherited skeletal muscle diseases, and Ullrich congenital muscular dystrophy (UCMD) is the most severe form. In addition to muscle weakness, UCMD patients show structural and functional changes of the tendon PCM. In this study, we investigated whether PCM alterations due to collagen VI mutations affect the response of tendon fibroblasts to mechanical stimulation. By taking advantage of human tendon cultures obtained from unaffected donors and from UCMD patients, we analyzed the morphological and functional properties of cellular mechanosensors. We found that the length of the primary cilia of UCMD cells was longer than that of controls. Unlike controls, in UCMD cells, both cilia prevalence and length were not recovered after mechanical stimulation. Accordingly, under the same experimental conditions, the activation of the Hedgehog signaling pathway, which is related to cilia activity, was impaired in UCMD cells. Finally, UCMD tendon cells exposed to mechanical stimuli showed altered focal adhesions, as well as impaired activation of Akt, ERK1/2, p38MAPK, and mechanoresponsive genes downstream of YAP. By exploring the response to mechanical stimulation, for the first time, our findings uncover novel unreported mechanistic aspects of the physiopathology of UCMD-derived tendon fibroblasts and point at a role for collagen VI in the modulation of mechanotransduction in tendons.

show abstract

Section: Discussionmentioning

confidence: 99%