Connexin 43 Modulation in Human Chondrocytes, Osteoblasts and Cartilage Explants: Implications for Inflammatory Joint Disorders.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, [2000-

Connexin 43*/metabolism ; Connexin 43*/genetics ; Chondrocytes*/metabolism ; Osteoblasts*/metabolism ; Tumor Necrosis Factor-alpha*/metabolism ; Tumor Necrosis Factor-alpha*/pharmacology ; Interleukin-1beta*/metabolism ; Interleukin-1beta*/pharmacology ; Osteoarthritis*/metabolism ; Osteoarthritis*/pathology ; Osteoarthritis*/genetics; Humans ; Synovial Fluid/metabolism ; Cartilage, Articular/metabolism ; Cartilage, Articular/pathology ; Cells, Cultured ; Aged ; Middle Aged ; Inflammation/metabolism ; Inflammation/genetics ; Inflammation/pathology ; Cartilage/metabolism ; Cartilage/pathology ; Joint Diseases/metabolism ; Joint Diseases/pathology ; Joint Diseases/genetics

Connexin 43 (Cx43) is crucial for the development and homeostasis of the musculoskeletal system, where it plays multifaceted roles, including intercellular communication, transcriptional regulation and influencing osteogenesis and chondrogenesis. Here, we investigated Cx43 modulation mediated by inflammatory stimuli involved in osteoarthritis, i.e., 10 ng/mL Tumor Necrosis Factor alpha (TNFα) and/or 1 ng/mL Interleukin-1 beta (IL-1β), in primary chondrocytes (CH) and osteoblasts (OB). Additionally, we explored the impact of synovial fluids from osteoarthritis patients in CH and cartilage explants, providing a more physio-pathological context. The effect of TNFα on Cx43 expression in cartilage explants was also assessed. TNFα downregulated Cx43 levels both in CH and OB (-73% and -32%, respectively), while IL-1β showed inconclusive effects. The reduction in Cx43 levels was associated with a significant downregulation of the coding gene GJA1 expression in OB only (-65%). The engagement of proteasome in TNFα-induced effects, already known in CH, was also observed in OB. TNFα treatment significantly decreased Cx43 expression also in cartilage explants. Of note, Cx43 expression was halved by synovial fluid in both CH and cartilage explants. This study unveils the regulation of Cx43 in diverse musculoskeletal cell types under various stimuli and in different contexts, providing insights into its modulation in inflammatory joint disorders.

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Ricerca Corrente L4169 and L4165 IRCCS Ospedale Galeazzi-Sant'Ambrogio Italian Ministry of Health

Keywords: Connexin 43; IL-1β; TNFα; cartilage explants; chondrocytes; osteoarthritis; osteoblasts; synovial fluid

0 (Connexin 43)
0 (Tumor Necrosis Factor-alpha)
0 (Interleukin-1beta)
0 (GJA1 protein, human)

Date Created: 20240810 Date Completed: 20240810 Latest Revision: 20240919

20240919

PMC11313680

10.3390/ijms25158547

39126115