Embryonic development of articular cartilage has not been well understood and the role of doublecortin (DCX) in determination of chondrocyte phenotype is unknown. Here, we use a DCX promoter-driven eGFP reporter mouse model to study the dynamic gene expression profiles in mouse embryonic handplates at E12.5 to E13.5 when the condensed mesenchymal cells differentiate into either endochondral chondrocytes or joint interzone cells. Illumina microarray analysis identified a variety of genes that were expressed differentially in the different regions of mouse handplate. The unique expression patterns of many genes were revealed. Cytl1 and 3110032G18RIK were highly expressed in the proximal region of E12.5 handplate and the carpal region of E13.5 handplate, whereas Olfr538, Kctd15, and Cited1 were highly expressed in the distal region of E12.5 and the metacarpal region of E13.5 handplates. There was an increasing gradient of Hrc expression in the proximal to distal direction in E13.5 handplate. Furthermore, when human DCX protein was expressed in human adipose stem cells, collagen II was decreased while aggrecan, matrilin 2, and GDF5 were increased during the 14-day pellet culture. These findings suggest that DCX may play a role in defining chondrocyte phenotype.
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http://dx.doi.org/10.3390/ijms15046941 | DOI Listing |
Biochem Pharmacol
January 2025
Department of Pharmacology, Nanjing Medical University, Nanjing 211166, PR China. Electronic address:
We have previously demonstrated that DEC1 promotes osteoblast differentiation. This study aims to evaluate the impact of DEC1 knockout on osteopenic activities, such as osteoclast differentiation and the expression of bone-degrading genes. To gain mechanistic insights, we employed both in vivo and in vitro experiments, utilizing cellular and molecular approaches, including osteoclast differentiation assays and RNA-seq in combination with ChIP-seq.
View Article and Find Full Text PDFNat Aging
January 2025
Discovery Center for Musculoskeletal Recovery, Schoen Adams Research Institute at Spaulding, Boston, MA, USA.
Female individuals who are post-menopausal present with higher incidence of knee osteoarthritis (KOA) than male counterparts; however, the mechanisms underlying this disparity are unknown. The most commonly used preclinical models lack human-relevant menopausal phenotypes, which may contribute to our incomplete understanding of sex-specific differences in KOA pathogenesis. Here we chemically induced menopause in middle-aged (14-16 months) C57/BL6N female mice.
View Article and Find Full Text PDFCommun Biol
January 2025
Guangdong Provincial Key Laboratory of Autophagy and Major Chronic Non-Communicable Diseases, Key Laboratory of Prevention and Management of Chronic Kidney Disease of Zhanjiang City, Institute of Nephrology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, Guangdong, China.
Mitochondrial homeostasis plays a crucial role in the pathogenesis of osteoarthritis (OA), a chronic musculoskeletal disorder characterized by articular cartilage degeneration and chondrocyte apoptosis. However, molecular mechanisms underlying the association between mitophagy and OA remain unclear. Here, we aimed to investigate the role of the autophagy receptor protein optineurin (OPTN) in OA, and explore the effects of dietary intervention on OA symptoms and its relationship with OPTN-mediated mitophagy.
View Article and Find Full Text PDFAm J Physiol Cell Physiol
January 2025
Division of Orthopedics, The third affiliated hospital of Sun Yat-sen university, Guangzhou 510530, China.
This study aimed to investigate the regulation of fibroblast phenotypes by MSCs delivering copper sulfide (CuS) nanoparticles (NPs) loaded with CDKN1A plasmids and their role in cartilage repair during osteoarthritis (OA). Single-cell RNA sequencing data from the GEO database were analyzed to identify subpopulations within the OA immune microenvironment. Quality control, filtering, PCA dimensionality reduction, and tSNE clustering were performed to obtain detailed cell subtypes.
View Article and Find Full Text PDFOsteoarthr Cartil Open
March 2025
Université de Lorraine, CNRS (French National Centre for Scientific Research), IMoPA (Molecular Engineering and Articular Physiopathology), F-54000, Nancy, France.
Objective: Osteoarthritis (OA) is the most common form of chronic joint disease, affecting mainly the elderly population. This disorder is caused by cartilage degeneration with complex changes in the chondrocyte phenotype. Inorganic pyrophosphate (PPi) was shown to counteract the detrimental effect of interleukin (IL)-1β challenging in an in vitro OA model based on rat articular chondrocytes.
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