{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["30(22)"],"submitter":["Pichler KM"],"pubmed_abstract":["<h4>Background/objectives</h4>Galectins contribute to the pathogenesis of osteoarthritis (OA) by amplifying inflammatory and catabolic signaling, yet targeted therapeutic approaches remain limited. Three Dimensional (3D) models offer a promising platform to study human OA pathophysiology and evaluate novel interventions.<h4>Methods</h4>We established 3D pellet cultures derived from human OA chondrocytes to investigate galectin-induced extracellular matrix (ECM) remodeling and the chondroprotective potential of phytochemicals. OA pellets were stimulated with individual galectins (Gal-1, -3, -4, -8) or a Gal-1/-3/-8 mixture, followed by co-treatment with Brazilin, Diacerein, Quercetin, Resveratrol, or Avocado-Soybean Unsaponifiables (ASU). Morphological, histological, biochemical, and gene expression analyses were performed to assess tissue integrity and molecular responses.<h4>Results</h4>Galectin treatment induced pronounced pellet shrinkage, matrix depletion, and upregulation of matrix-degrading enzymes (MMP-1, MMP-3, MMP-13, ADAMTS-4), while suppressing matrix synthesis markers (COL2A1, COL1A1), highlighting their cooperative catabolic effects. Co-treatment with phytochemicals conferred differential protection: Brazilin and Diacerein most consistently preserved pellet size, reduced matrix-degrading gene expression, and attenuated pro-MMP-13 secretion. Resveratrol restored histological matrix density but failed to suppress pro-MMP-13 secretion. Notably, no phytochemical fully restored COL2A1 expression under galectin-induced stress.<h4>Conclusions</h4>Our study identifies Brazilin, Diacerein, and Resveratrol as promising modulators of galectin-driven cartilage degeneration and demonstrates the translational potential of patient-derived chondrogenic pellets as a human-relevant platform for preclinical drug evaluation in OA. The 3D culture effectively recapitulates key aspects of OA pathophysiology and offers a robust system to advance therapeutic discovery targeting ECM remodeling."],"journal":["Molecules (Basel, Switzerland)"],"pagination":["4391"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12655804"],"repository":["biostudies-literature"],"pubmed_title":["Targeting the Galectin Axis in Osteoarthritis: Chondroprotective Effects of Dietary and Pharmacological Phytochemicals."],"pmcid":["PMC12655804"],"pubmed_authors":["Rothbauer M","Schmidt S","Alphonsus J","Pichler KM","Kaltner H","Windhager R","Rodriguez Molina B","Toegel S","Kottinger S"],"additional_accession":[]},"is_claimable":false,"name":"Targeting the Galectin Axis in Osteoarthritis: Chondroprotective Effects of Dietary and Pharmacological Phytochemicals.","description":"<h4>Background/objectives</h4>Galectins contribute to the pathogenesis of osteoarthritis (OA) by amplifying inflammatory and catabolic signaling, yet targeted therapeutic approaches remain limited. Three Dimensional (3D) models offer a promising platform to study human OA pathophysiology and evaluate novel interventions.<h4>Methods</h4>We established 3D pellet cultures derived from human OA chondrocytes to investigate galectin-induced extracellular matrix (ECM) remodeling and the chondroprotective potential of phytochemicals. OA pellets were stimulated with individual galectins (Gal-1, -3, -4, -8) or a Gal-1/-3/-8 mixture, followed by co-treatment with Brazilin, Diacerein, Quercetin, Resveratrol, or Avocado-Soybean Unsaponifiables (ASU). Morphological, histological, biochemical, and gene expression analyses were performed to assess tissue integrity and molecular responses.<h4>Results</h4>Galectin treatment induced pronounced pellet shrinkage, matrix depletion, and upregulation of matrix-degrading enzymes (MMP-1, MMP-3, MMP-13, ADAMTS-4), while suppressing matrix synthesis markers (COL2A1, COL1A1), highlighting their cooperative catabolic effects. Co-treatment with phytochemicals conferred differential protection: Brazilin and Diacerein most consistently preserved pellet size, reduced matrix-degrading gene expression, and attenuated pro-MMP-13 secretion. Resveratrol restored histological matrix density but failed to suppress pro-MMP-13 secretion. Notably, no phytochemical fully restored COL2A1 expression under galectin-induced stress.<h4>Conclusions</h4>Our study identifies Brazilin, Diacerein, and Resveratrol as promising modulators of galectin-driven cartilage degeneration and demonstrates the translational potential of patient-derived chondrogenic pellets as a human-relevant platform for preclinical drug evaluation in OA. The 3D culture effectively recapitulates key aspects of OA pathophysiology and offers a robust system to advance therapeutic discovery targeting ECM remodeling.","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Nov","modification":"2026-05-19T03:27:52.705Z","creation":"2026-05-19T03:12:26.377Z"},"accession":"S-EPMC12655804","cross_references":{"pubmed":["41302448"],"doi":["10.3390/molecules30224391"]}}