The C-terminal domain of connexin43 modulates cartilage structure via chondrocyte phenotypic changes.
Chondrocytes in cartilage and bone cells population express connexin43 (Cx43) and gap junction intercellular communication (GJIC) is essential to synchronize cells for coordinated electrical, mechanical, metabolic and chemical communication in both tissues. Reduced Cx43 connectivity decreases chondrocyte differentiation and defective Cx43 causes skeletal defects. The carboxy terminal domain (CTD) of Cx43 is located in the cytoplasmic side and is key for protein functions. Here we demonstrated that chondrocytes from the CTD-deficient mice, K258stop/Cx43KO and K258stop/K258stop, have reduced GJIC, increased rates of proliferation and reduced expression of collagen type II and proteoglycans. We observed that CTD-truncated mice were significantly smaller in size. Together these results demonstrated that the deletion of the CTD negatively impacts cartilage structure and normal chondrocyte phenotype. These findings suggest that the proteolytic cleavage of the CTD under pathological conditions, such as under the activation of metalloproteinases during tissue injury or inflammation, may account for the deleterious effects of Cx43 in cartilage and bone disorders such as osteoarthritis.
CellCOM-SB Research Group, Instituto de Investigación Biomédica de A Coruña (INIBIC), CH-Universitario A Coruña (XXIAC), University of A Coruña, Servizo Galego de Saúde (SERGAS), Xubias de Arriba, 84 15006 A Coruña, Spain.
Raquel
R
Gago-Fuentes
Department of Cellular and Physiological Sciences, The Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada, V6T 1Z3.
John F
JF
Bechberger
CellCOM-SB Research Group, Instituto de Investigación Biomédica de A Coruña (INIBIC), CH-Universitario A Coruña (XXIAC), University of A Coruña, Servizo Galego de Saúde (SERGAS), Xubias de Arriba, 84 15006 A Coruña, Spain.
Marta
M
Varela-Eirin
CellCOM-SB Research Group, Instituto de Investigación Biomédica de A Coruña (INIBIC), CH-Universitario A Coruña (XXIAC), University of A Coruña, Servizo Galego de Saúde (SERGAS), Xubias de Arriba, 84 15006 A Coruña, Spain.
Adrian
A
Varela-Vazquez
CellCOM-SB Research Group, Instituto de Investigación Biomédica de A Coruña (INIBIC), CH-Universitario A Coruña (XXIAC), University of A Coruña, Servizo Galego de Saúde (SERGAS), Xubias de Arriba, 84 15006 A Coruña, Spain.
Benigno
B
Acea
CellCOM-SB Research Group, Instituto de Investigación Biomédica de A Coruña (INIBIC), CH-Universitario A Coruña (XXIAC), University of A Coruña, Servizo Galego de Saúde (SERGAS), Xubias de Arriba, 84 15006 A Coruña, Spain.
Eduardo
E
Fonseca
Department of Cellular and Physiological Sciences, The Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada, V6T 1Z3.
Christian C
CC
Naus
CellCOM-SB Research Group, Instituto de Investigación Biomédica de A Coruña (INIBIC), CH-Universitario A Coruña (XXIAC), University of A Coruña, Servizo Galego de Saúde (SERGAS), Xubias de Arriba, 84 15006 A Coruña, Spain.
Maria D
MD
Mayan
D000818:Animals; D015415:Biomarkers; D002358:Cartilage, Articular / Q000166:cytology* / Q000378:metabolism* / Q000473:pathology; D019902:Chondrocytes / Q000378:metabolism*; D018031:Connexin 43 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D007150:Immunohistochemistry; D051379:Mice; D010003:Osteoarthritis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D054730:Protein Interaction Domains and Motifs / Q000235:genetics*; D059748:Proteolysis
D015415:Biomarkers; D018031:Connexin 43
C-terminal domain of Cx43; articular cartilage; chondrocyte; connexin43; osteoarthritis
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