Autophagy-related proteases accompany the transition of pre-chondrogenic cells into chondroblasts

Ramesova, Alice; Švandová, Eva; Veselá, Barbora; Vacek, L; Lesot, Hervé; Matalová, Eva

doi:10.1016/j.aanat.2021.151781

Cited by 5 publications

(5 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been shown, in osteogenic differentiation [ 46 ], that transient autophagy activation supplies cells with energy, confirming that autophagy is fundamental in the initial phase because it fuels the cells that are then prone to differentiation. Interestingly, this evidence is also in line with papers [ 12 , 13 ] that studied the developmental of cartilage using in vivo animal models, demonstrating that the initial induction of autophagy played a peculiar role in coordinating chondrocyte differentiation and pre-chondrogenic cells transitioning into chondroblasts. Moreover, it has been shown that autophagy protects the cells from senescence [ 39 ], contributes to their rejuvenation [ 40 ], and shows a potential key contribution to hASCs’ therapeutic action [ 20 , 47 ] by providing a vital activity to cells.…”

Section: Resultssupporting

confidence: 87%

“…It has been shown, using the zebrafish joint formation model and murine limbs at prenatal stages, that autophagy coordinates chondrocyte differentiation and the transition of prechondrogenic cells into chondroblasts in vivo [ 12 , 13 ]. It has been confirmed in vitro that autophagy plays an indispensable role in the transition of mesenchymal stromal cells (MSCs) to proliferative chondrocytes [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

“…It has been shown that autophagy activation contributes to suppressing the chondrogenesis of MSCs, while the reduction of the autophagic process contributes to the activation of MSCs chondrogenesis [ 25 ]. In fact, the delay of cartilage development is strictly related to the inhibition of autophagy [ 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Autophagy Is a Crucial Path in Chondrogenesis of Adipose-Derived Mesenchymal Stromal Cells Laden in Hydrogel

Gabusi

Lenzi

Manferdini

et al. 2022

Gels

View full text Add to dashboard Cite

Autophagy is a cellular process that contributes to the maintenance of cell homeostasis through the activation of a specific path, by providing the necessary factors in stressful and physiological situations. Autophagy plays a specific role in chondrocyte differentiation; therefore, we aimed to analyze this process in adipose-derived mesenchymal stromal cells (ASCs) laden in three-dimensional (3D) hydrogel. We analyzed chondrogenic and autophagic markers using molecular biology, immunohistochemistry, and electron microscopy. We demonstrated that ASCs embedded in 3D hydrogel showed an increase expression of typical autophagic markers Beclin 1, LC3, and p62, associated with clear evidence of autophagic vacuoles in the cytoplasm. During ASCs chondrogenic differentiation, we showed that autophagic markers declined their expression and autophagic vesicles were rare, while typical chondrogenic markers collagen type 2, and aggrecan were significantly increased. In line with developmental animal models of cartilage, our data showed that in a 3D hydrogel, ASCs increased their autophagic features. This path is the fundamental prerequisite for the initial phase of differentiation that contributes to fueling the cells with energy and factors necessary for chondrogenic differentiation.

show abstract

Section: Resultssupporting

confidence: 87%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Autophagy Is a Crucial Path in Chondrogenesis of Adipose-Derived Mesenchymal Stromal Cells Laden in Hydrogel

Gabusi

Lenzi

Manferdini

et al. 2022

Gels

View full text Add to dashboard Cite

show abstract

“…CTSD's single mutation or partial deletion could induce lysosomal dysfunction or even cell death, 63 resulting in a variety of autophagy‐mediated multisystem diseases, such as stroke 64 and non‐alcoholic fatty liver disease 65 . Recent studies have also found that the expression level of autophagy‐related proteases such as CTSD was increased during the development of phalangeal cartilage in mice, 66 suggesting that CTSD contributed to the cartilage development as a critical regulator of autophagy.…”

Section: Discussionmentioning

confidence: 99%

Autophagy inhibition mediated by intrauterinemiR‐1912‐3p/CTSDprogramming participated in the susceptibility to osteoarthritis induced by prenatal dexamethasone exposure in male adult offspring rats

Shi

Zhang

et al. 2023

The FASEB Journal

View full text Add to dashboard Cite

Autophagy inhibition is known to be involved in the development of adult osteoarthritis. Dexamethasone, as a synthetic glucocorticoid, is widely used for premature delivery and related pregnancy diseases in clinics. We have previously shown that prenatal dexamethasone exposure (PDE) was associated with increased susceptibility to postnatal osteoarthritis in offspring. However, whether the occurrence of fetal-originated adult osteoarthritis induced by PDE is related to autophagy remains unclear. In this study, we first found that PDE could increase the mRNA and protein expression of cartilage matrix-degrading enzymes (MMP3, MMP13, and ADAMTS5) and decrease the cartilage matrix contents in adult offspring, and the in vitro results suggested that this might be related to the autophagy inhibition of chondrocytes. Further, we demonstrated a persistent autophagy inhibition with autolysosome accumulation, low expression of cathepsin D (CTSD), increased H3K9ac level, and expression of miR-1912-3p in the cartilage of PDE offspring from fetus to adulthood. In vitro experiments showed that dexamethasone inhibited autophagy flux and CTSD expression in fetal chondrocytes, while overexpression of CTSD could alleviate the inhibition of autophagic flux induced by dexamethasone. Finally, we confirmed that dexamethasone increased the H3K9ac level and expression of miR-1912-3p through activation of the glucocorticoid receptor (GR), resulting in the decreased expression of CTSD and inhibition of autophagy flux in fetal chondrocytes. In conclusion, intrauterine miR-1912-3p/ CTSD programming-mediated autophagy inhibition promoted the susceptibility to osteoarthritis in PDE adult offspring rats. This study provides new ideas for exploring early prevention and therapeutic targets in fetal-originated osteoarthritis.

show abstract

“…High expression of HTC cells is related to cartilage degeneration of OA 66 , which might be accompanied by the increase of ACT. CTSD, associated with cartilage development, shows an increase in expression level during the transformation of prochondroblasts into chondroblasts in vivo 67 . Differential expression of AGT and CTSD in Homc cells between OA samples and normal samples might indicate that the development and metabolic disorder of chondrocytes are involved in the progress of OA 23 ,which is consistent with our results.…”

Section: Discussionmentioning

confidence: 99%

Integrated single-cell and bulk RNA sequencing analysis identified pyroptosis-related signature for diagnosis and prognosis in osteoarthritis

Chen,

Zhang,

et al. 2023

Sci Rep

View full text Add to dashboard Cite

Osteoarthritis (OA), a degenerative disease of the joints, has one of the highest disability rates worldwide. This study investigates the role of pyroptosis-related genes in osteoarthritis and their expression in different chondrocyte subtypes at the individual cell level. Using OA-related datasets for single-cell RNA sequencing and RNA-seq, the study identified PRDEGs and DEGs and conducted Cox regression analysis to identify independent prognostic factors for OA. CASP6, NOD1, and PYCARD were found to be prognostic factors. Combined Weighted Gene Correlation Network Analysis with PPI network, a total of 15 hub genes related to pyroptosis were involved in the notch and oxidative phosphorylation pathways, which could serve as biomarkers for the diagnosis and prognosis of OA patients. The study also explored the heterogeneity of chondrocytes between OA and normal samples, identifying 19 single-cell subpopulation marker genes that were significantly different among 7 chondrocyte cell clusters. AGT, CTSD, CYBC, and THYS1 were expressed differentially among different cell subpopulations, which were associated with cartilage development and metabolism. These findings provide valuable insights into the molecular mechanisms underlying OA and could facilitate the development of new therapeutic strategies for this debilitating disease.

show abstract

Autophagy-related proteases accompany the transition of pre-chondrogenic cells into chondroblasts

Cited by 5 publications

References 40 publications

Autophagy Is a Crucial Path in Chondrogenesis of Adipose-Derived Mesenchymal Stromal Cells Laden in Hydrogel

Autophagy Is a Crucial Path in Chondrogenesis of Adipose-Derived Mesenchymal Stromal Cells Laden in Hydrogel

Autophagy inhibition mediated by intrauterinemiR‐1912‐3p/CTSDprogramming participated in the susceptibility to osteoarthritis induced by prenatal dexamethasone exposure in male adult offspring rats

Integrated single-cell and bulk RNA sequencing analysis identified pyroptosis-related signature for diagnosis and prognosis in osteoarthritis

Contact Info

Product

Resources

About