{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nOsteoglycin (OGN), also known as mimecan, is emerging as a multifaceted regulator of tissue growth and homeostasis. It is secreted by a subset of natural killer cells at the maternal–fetal interface, where it contributes to local growth‐promoting functions essential for normal fetal development."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In addition, studies in colorectal adenoma indicate that loss of mimecan/OGN expression accompanies early neoplastic transformation, suggesting its putative role as a guardian of tissue architecture."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " \n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the context of tumorigenesis, OGN appears to display dual functions depending on the tissue and microenvironment. Its altered expression is linked to the progression of colorectal cancer, where distinct expression patterns correlate with clinical behavior"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ", and it may modulate local immune responses within the tumor microenvironment."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " In malignant meningioma and pancreatic cancer, OGN overexpression stimulates oncogenic pathways—such as mTOR signaling via upregulation of ID4—thereby promoting proliferation, migration, and invasion while inhibiting apoptosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nOGN is also instrumental in connective tissue remodeling and skeletal health. A circular RNA (circ_0076906) was shown to enhance osteogenic differentiation of human mesenchymal stem cells by sponging miR‐1305 and consequently upregulating OGN, which contributes to bone formation and may alleviate osteoporosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Moreover, circulating OGN correlates with muscle–bone interactions, underscoring its significance in maintaining proper skeletal metabolism."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nCardiovascular integrity and vascular extracellular matrix organization are critically influenced by OGN. As a small leucine‐rich proteoglycan, OGN regulates collagen fibrillogenesis and helps maintain vessel wall architecture."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " In the heart, increased OGN expression is observed in response to pressure overload where it modulates fibrosis, inflammation, and cardiac remodeling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " In ischemic settings, OGN influences angiogenesis"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": ", while in vascular smooth muscle cells, its downregulation promotes proliferation and migration via activation of VEGFR–AKT/ERK signaling cascades, a mechanism relevant to aortic dissection."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": " Furthermore, clinical investigations in hypertensive and atherosclerotic patients support the role of circulating OGN in arterial stiffness and plaque vulnerability."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "14", "end_ref": "19"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its roles in structural and oncogenic processes, OGN contributes to neuromodulation, metabolism, and other organ-specific functions. In neural cells, OGN enhances IGF‐2/IGFBP2–mediated neurite outgrowth, indicating a role in neuronal plasticity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "20"}]}, {"type": "t", "text": " In adipose tissue, mimecan acts as a satiety hormone, reducing food intake and body weight independent of leptin signaling"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "21"}]}, {"type": "t", "text": ", while its abundant expression in the cochlea suggests specialized functions, even though its absence does not compromise hearing thresholds."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "22"}]}, {"type": "t", "text": " Moreover, OGN may be upregulated during hyperglycemia to potentiate insulin action"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "23"}]}, {"type": "t", "text": "and is implicated in the early pathophysiological changes of diabetic nephropathy as an osteoinductive factor."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "24"}]}, {"type": "t", "text": " In pulmonary fibrosis associated with interstitial lung disease, miR‐140-mediated downregulation of OGN reduces fibroblast proliferation and activates the Wnt signaling pathway"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "25"}]}, {"type": "t", "text": ", while serum OGN levels have prognostic value in chronic kidney disease."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "26"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Binqing Fu, Yonggang Zhou, Xiang Ni, et al. 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