TGFβ/BMP Signaling Pathway in Cartilage Homeostasis

Thielen, N.; Kraan, P.M. van der; Caam, A. van

doi:10.3390/cells8090969

Cited by 201 publications

(183 citation statements)

References 252 publications

(340 reference statements)

Supporting

Mentioning

181

Contrasting

Unclassified

Order By: Relevance

“…Several signaling pathways are involved in chondrogenesis, including TGF-β signaling 43 and Wnt signaling 44,45 . TGF-β is a multifunctional cytokine found in bone, cartilage matrix, and platelets, and it induces chondrocyte proliferation and maturation 28,46 .…”

Section: Discussionmentioning

confidence: 99%

Shaking culture enhances chondrogenic differentiation of mouse induced pluripotent stem cell constructs

Limraksasin

Kosaka

Zhang

et al. 2020

Sci Rep

View full text Add to dashboard Cite

Mechanical loading on articular cartilage induces various mechanical stresses and strains. In vitro hydrodynamic forces such as compression, shear and tension impact various cellular properties including chondrogenic differentiation, leading us to hypothesize that shaking culture might affect the chondrogenic induction of induced pluripotent stem cell (iPSC) constructs. Three-dimensional mouse iPSC constructs were fabricated in a day using U-bottom 96-well plates, and were subjected to preliminary chondrogenic induction for 3 days in static condition, followed by chondrogenic induction culture using a see-saw shaker for 17 days. After 21 days, chondrogenically induced iPSC (CI-iPSC) constructs contained chondrocyte-like cells with abundant ECM components. Shaking culture significantly promoted cell aggregation, and induced significantly higher expression of chondrogenic-related marker genes than static culture at day 21. Immunohistochemical analysis also revealed higher chondrogenic protein expression. Furthemore, in the shaking groups, CI-iPSCs showed upregulation of TGF-β and Wnt signaling-related genes, which are known to play an important role in regulating cartilage development. These results suggest that shaking culture activates TGF-β expression and Wnt signaling to promote chondrogenic differentiation in mouse iPSCs in vitro. Shaking culture, a simple and convenient approach, could provide a promising strategy for iPSC-based cartilage bioengineering for study of disease mechanisms and new therapies.

show abstract

Section: Discussionmentioning

confidence: 99%

Shaking culture enhances chondrogenic differentiation of mouse induced pluripotent stem cell constructs

Limraksasin

Kosaka

Zhang

et al. 2020

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Altered post-translational modifications may also play a role in OA [44]. TFs such as AP-1, SMAD3/4, hypoxia-inducible factor (HIF), and C/EBP are targets of post-translational modifications [45].…”

Section: Transcription Factors In Oamentioning

confidence: 99%

Transcription Factors in Cartilage Homeostasis and Osteoarthritis

Neefjes

Caam

Kraan

2020

Biology

Self Cite

View full text Add to dashboard Cite

Osteoarthritis (OA) is the most common degenerative joint disease, and it is characterized by articular cartilage loss. In part, OA is caused by aberrant anabolic and catabolic activities of the chondrocyte, the only cell type present in cartilage. These chondrocyte activities depend on the intra- and extracellular signals that the cell receives and integrates into gene expression. The key proteins for this integration are transcription factors. A large number of transcription factors exist, and a better understanding of the transcription factors activated by the various signaling pathways active during OA can help us to better understand the complex etiology of OA. In addition, establishing such a profile can help to stratify patients in different subtypes, which can be a very useful approach towards personalized therapy. In this review, we discuss crucial transcription factors for extracellular matrix metabolism, chondrocyte hypertrophy, chondrocyte senescence, and autophagy in chondrocytes. In addition, we discuss how insight into these factors can be used for treatment purposes.

show abstract

“…IPA miRNA 'Target Filter and Expression Pairing' identified 31 potential target genes. IPA core analysis of these genes revealed canonical pathways associated with cartilage physiology, such as role of chondrocytes in rheumatoid arthritis, OA-related pathways and bone morphogenic protein (BMP) signalling, all of which have been reported to change with ageing [56,71,72]. Moreover, top diseases and disorders linked to these genes, as identified by IPA, included skeletal and muscular disorders and connective tissue disorders.…”

Section: Discussionmentioning

confidence: 99%

Small Non-Coding RNAome of Ageing Chondrocytes

Balaskas

Green

Haqqi

et al. 2020

IJMS

View full text Add to dashboard Cite

Ageing is a leading risk factor predisposing cartilage to osteoarthritis. However, little research has been conducted on the effect of ageing on the expression of small non-coding RNAs (sncRNAs). RNA from young and old chondrocytes from macroscopically normal equine metacarpophalangeal joints was extracted and subjected to small RNA sequencing (RNA-seq). Differential expression analysis was performed in R using package DESeq2. For transfer RNA (tRNA) fragment analysis, tRNA reads were aligned to horse tRNA sequences using Bowtie2 version 2.2.5. Selected microRNA (miRNAs or miRs) and small nucleolar RNA (snoRNA) findings were validated using real-time quantitative Polymerase Chain Reaction (qRT-PCR) in an extended cohort of equine chondrocytes. tRNA fragments were further investigated in low- and high-grade OA human cartilage tissue. In total, 83 sncRNAs were differentially expressed between young and old equine chondrocytes, including miRNAs, snoRNAs, small nuclear RNAs (snRNAs), and tRNAs. qRT-PCR analysis confirmed findings. tRNA fragment analysis revealed that tRNA halves (tiRNAs), tiRNA-5035-GluCTC and tiRNA-5031-GluCTC-1 were reduced in both high grade OA human cartilage and old equine chondrocytes. For the first time, we have measured the effect of ageing on the expression of sncRNAs in equine chondrocytes. Changes were detected in a number of different sncRNA species. This study supports a role for sncRNAs in ageing cartilage and their potential involvement in age-related cartilage diseases.

show abstract

TGFβ/BMP Signaling Pathway in Cartilage Homeostasis

Cited by 201 publications

References 252 publications

Shaking culture enhances chondrogenic differentiation of mouse induced pluripotent stem cell constructs

Shaking culture enhances chondrogenic differentiation of mouse induced pluripotent stem cell constructs

Transcription Factors in Cartilage Homeostasis and Osteoarthritis

Small Non-Coding RNAome of Ageing Chondrocytes

Contact Info

Product

Resources

About