{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Biglycan (BGN) is a multifunctional small leucine‐rich proteoglycan that plays diverse roles in regulating extracellular matrix organization, cell signaling, and innate immune responses across multiple tissues. In the innate immune system, soluble biglycan acts as an endogenous danger signal by binding to Toll‐like receptors 2 and 4, which leads to the activation of the NLRP3 inflammasome and subsequent secretion of inflammatory mediators such as interleukin‐1β (IL‑1β)."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In parallel, biglycan modulates tissue regeneration and bone homeostasis; it facilitates bone formation by enhancing binding of bone morphogenetic protein‑4 (BMP‑4) to its receptors and by promoting canonical Wnt signaling through interactions with Wnt3a and its coreceptor LRP6, thus influencing osteoblast differentiation and activity."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "5"}]}, {"type": "t", "text": " Aberrant expression of biglycan is associated with defects in mineralization, as seen in dentinogenesis imperfecta models where increased levels correlate with impaired coalescence of calcospherites in dentin."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " In musculoskeletal tissues, biglycan can compensate for alterations in related proteoglycans—its expression is enhanced in decorin‐deficient tendons, suggesting a role in maintaining collagen fibrillogenesis and mechanical integrity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Furthermore, biglycan serves as a ligand for receptors beyond TLRs; for instance, interaction with the mannose receptor mediates anti‐inflammatory cytokine production in dendritic cells"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": ", and binding to α‑dystroglycan supports extracellular matrix anchorage at the muscle membrane."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " In addition to these signaling roles, biglycan directly organizes matrix components by promoting the assembly of collagen VI into hexagonal networks, thereby contributing to the structural integrity of tissues."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings underscore biglycan’s critical dual function as both a structural organizer of the extracellular matrix and a modulator of cell signaling pathways—ranging from inflammatory responses to osteogenesis—thereby highlighting its importance in tissue repair, regeneration, and homeostasis.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Andrea Babelova, Kristin Moreth, Wasiliki Tsalastra-Greul, et al. 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