Dataset Information

Single-cell sequencing of murine articular cartilage

ABSTRACT: Osteoarthritis (OA) is a degenerative joint disease characterized by progressive cartilage loss, bone remodeling, synovial inflammation, and significant joint pain, often resulting in disability. Injury to the synovial joint such as the anterior cruciate ligament (ACL) tear is the major cause of OA in young adults. Currently, there are no approved therapies available to prevent joint degeneration or rebuild articular cartilage destroyed by OA, primarily because our understanding of the cellular and molecular changes that contribute to joint damage is very limited. The synovial joint is a complex structure composed of several tissues including articular cartilage, subchondral bone, synovium, synovial fluid, and tensile tissues including tendons and ligaments. In the present study, using single-cell RNA sequencing (scRNA-seq), we examined the cellular heterogeneity in articular cartilage from mouse knee joints and determined the knee joint injury-induced early molecular changes in the chondrocytes that could contribute to OA.

ORGANISM(S): Mus musculus

PROVIDER: GSE172500 | GEO | 2021/06/19

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:As the most common degenerative joint disease, osteoarthritis (OA) contributes significantly to pain and disability during aging. Several genes of interest involved in articular cartilage damage in OA have been identified. However, the direct causes of OA are poorly understood. Evaluating the public human RNA-seq dataset showed that Cbfβ, (subunit of a heterodimeric Cbfβ/Runx1,Runx2, or Runx3 complex) expression is decreased in the cartilage of patients with OA. Here, we found that the chondrocyte-specific deletion of Cbfβ in tamoxifen-induced Cbfβf/fCol2α1-CreERT mice caused a spontaneous OA phenotype, worn articular cartilage, increased inflammation, and osteophytes. RNA-sequencing analysis showed that Cbfβ deficiency in articular cartilage resulted in reduced cartilage regeneration, increased canonical Wnt signaling and inflammatory response, and decreased Hippo/YAP signaling and TGF-β signaling. Immunostaining and western blot validated these RNA-seq analysis results. ACLT surgery-induced OA decreased Cbfβ and Yap expression and increased active β-catenin expression in articular cartilage, while local AAV-mediated Cbfβ overexpression promoted Yap expression and diminished active β-catenin expression in OA lesions. Remarkably, AAV-mediated Cbfβ overexpression in knee joints of mice with OA showed the significant protective effect of Cbfβ on articular cartilage in the ACLT OA mouse model. Overall, this study, using loss-of-function and gain-of-function approaches, uncovered that low expression of Cbfβ may be the cause of OA. Moreover, Local admission of Cbfβ may rescue and protect OA through decreasing Wnt/β-catenin signaling, and increasing Hippo/Yap signaling and TGFβ/Smad2/3 signaling in OA articular cartilage, indicating that local Cbfβ overexpression could be an effective strategy for treatment of OA. Using unbiased genome-wide RNA-seq data from Cbfβf/f;Col2α1-Cre hip joint articular cartilage and Cbfβf/f;Aggrecan-cre knee joint articular cartilage and their controls, we examined Cbfβ-mediated transcriptional targets for articular cartilage regeneration in OA.

Dataset Information

Single-cell sequencing of murine articular cartilage

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets