A5103191826- Osteoarthritis Treatment and Mechanisms
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Cell Adhesion Molecules Research
- Cancer-related molecular mechanisms research
- Genomics and Chromatin Dynamics
- RNA Research and Splicing
- Prostate Cancer Treatment and Research
- MicroRNA in disease regulation
- Developmental Biology and Gene Regulation
- Congenital heart defects research
- Epigenetics and DNA Methylation
- Immune Cell Function and Interaction
- interferon and immune responses
- Neurogenesis and neuroplasticity mechanisms
- Hepatitis C virus research
- IL-33, ST2, and ILC Pathways
- Protease and Inhibitor Mechanisms
- NF-κB Signaling Pathways
- Acute Myeloid Leukemia Research
- Hepatitis B Virus Studies
- T-cell and B-cell Immunology
- Knee injuries and reconstruction techniques
- Pancreatic function and diabetes
- Connective tissue disorders research
- Bone Metabolism and Diseases
Children's Hospital of Philadelphia
2018-2025
University of Pennsylvania
2025
Université Laval
2020-2023
Cleveland Clinic Lerner College of Medicine
2008-2022
Centre Hospitalier Régional de Namur
2021-2022
Centre hospitalier universitaire de Québec
2020
Cleveland Clinic
2005-2019
RELX Group (United States)
2018
Salk Institute for Biological Studies
2016
UC San Diego Health System
2016
The identification of mutations in the SRY-related SOX9 gene patients with campomelic dysplasia, a severe skeletal malformation syndrome, and abundant expression Sox9 mouse chondroprogenitor cells fully differentiated chondrocytes during embryonic development have suggested hypothesis that might play role chondrogenesis. Our previous experiments (Col2a1) for collagen II, an early marker chondrocyte differentiation, identified minimal DNA element intron 1 which directs chondrocyte-specific...
To assess the role of transcription factor Sox9 in cartilage formation we have compared expression pattern and Col2a1 at various stages mouse embryonic development. Expression colocalized with all chondroprogenitor cells. In sclerotomal compartment somites onset preceded that Col2a1. A perfect correlation was also seen between high levels chondrocytic However, no detected hypertrophic chondrocytes; only low RNA were found upper zone. Coexpression notochord. At E11.5 brain spinal neural tube...
The long-term integrity of an articulating joint is dependent upon the nourishment its cartilage component and protection surface from friction-induced wear. Loss-of-function mutations in lubricin (a secreted glycoprotein encoded by gene PRG4) cause human autosomal recessive disorder camptodactyly-arthropathy-coxa vara-pericarditis syndrome (CACP). A major feature CACP precocious failure. In order to delineate mechanism which protects joints, we studied expression Prg4 mRNA during mouse...
The long-term integrity of an articulating joint is dependent upon the nourishment its cartilage component and protection surface from friction-induced wear. Loss-of-function mutations in lubricin (a secreted glycoprotein encoded by gene PRG4) cause human autosomal recessive disorder camptodactyly-arthropathy-coxa vara-pericarditis syndrome (CACP). A major feature CACP precocious failure. In order to delineate mechanism which protects joints, we studied expression Prg4 mRNA during mouse...
The Sry-related high-mobility-group box transcription factor Sox9 recruits the redundant L-Sox5 and Sox6 proteins to effect chondrogenesis, but mode of action trio remains unclear. We identify here a highly conserved 359-bp sequence 10 kb upstream Agc1 gene for aggrecan, most essential cartilage proteoglycan key marker chondrocyte differentiation. This directs expression minimal promoter in both embryonic adult transgenic mice, manner that matches expression. chondrogenic is required...
SOX9 is a transcriptional activator required for chondrogenesis, and SOX5 SOX6 are closely related DNA-binding proteins that critically enhance its function. We use here genome-wide approaches to gain novel insights into the full spectrum of target genes modes action this chondrogenic trio. Using RCS cell line as faithful model proliferating/early prehypertrophic growth plate chondrocytes, we uncover bind thousands genomic sites, frequently most efficiently near each other. recognizes pairs...
Significance Cartilage is essential in vertebrate development and adulthood. growth plates ensure skeletal until closing at puberty, articular cartilage ensures lifelong structural functional integrity of joints. Chondrocytes build development, governed by the transcription factor SOX9. Using mouse models transcriptome profiling approaches, we show here that SOX9 also has key roles to maintain open postnatally protect adult from osteoarthritic degradation. In particular, safeguards lineage...
Sox9 is a high-mobility-group domain-containing transcription factor required for chondrocyte differentiation and cartilage formation. We used yeast two-hybrid method based on Son of Sevenless (SOS) recruitment to screen cDNA library found that the catalytic subunit cyclic AMP (cAMP)-dependent protein kinase A (PKA-Cα) interacted specifically with SOX9. Next we two consensus PKA phosphorylation sites within SOX9 could be phosphorylated by in vitro PKA-Cα vivo. In COS-7 cells cotransfected...
The inflammatory cytokines interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-α) strongly inhibit the expression of genes for cartilage extracellular matrix proteins. We have recently obtained genetic evidence indicating that high mobility group domain containing transcription factor Sox9 is required formation chondrocyte-specific including gene type II collagen (Col2a1). show here IL-1 TNF-α cause a marked rapid decrease in levels ofSox9 mRNA and/or protein chondrocytes. A role NFκB...
The group C of Sry-related high-mobility (HMG) box (Sox) transcription factors has three members in most vertebrates: Sox4, Sox11 and Sox12. Sox4 have key roles cardiac, neuronal other major developmental processes, but their molecular many lineages the Sox12 remain largely unknown. We show here that genes are co-expressed at high levels mesenchymal tissues developing mouse, variable relative tissues. proteins conserved remarkable identity through evolution HMG DNA-binding domain C-terminal...
During organogenesis, neural and mesenchymal progenitor cells give rise to many cell lineages, but their molecular requirements for self-renewal lineage decisions are incompletely understood. In this study, we show that survival critically relies on the redundantly acting SoxC transcription factors Sox4, Sox11 Sox12. The more alleles deleted in mouse embryos, severe widespread organ hypoplasia is. triple-null embryos die at midgestation unturned tiny, with normal patterning specification,...