{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nOSTN—also known as osteocrin—is a secreted protein that plays distinct roles in skeletal and neural tissues. In bone, OSTN is uniquely expressed in osteoblasts and young osteocytes, where it is tightly regulated by vitamin D and developmental cues, and functions to modulate mineralization by interacting with the natriuretic peptide system (binding to NPR‐C to augment CNP signaling) and promoting osteocyte dendrite formation via targets of key transcription factors such as Sp7. In the primate brain, OSTN has been repurposed as an activity‐dependent secreted factor that limits dendritic overgrowth, and genetic data further link higher OSTN expression with reduced tau pathology in Alzheimer’s disease in a female‐specific manner."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its skeletal and neuronal actions, OSTN—referred to as Musclin when derived from muscle—functions as a myokine regulated by nutritional and hormonal signals (notably via Foxo1). Alterations in Musclin levels have been implicated in multiple cardiometabolic contexts: diminished expression in wasting skeletal muscle is linked to exacerbated cardiac dysfunction and fibrosis under pressure overload, while decreased levels correlate with diabetic complications, including diabetic nephropathy. Furthermore, Musclin exerts protective effects on the liver by alleviating palmitate-induced endoplasmic reticulum stress and lipid deposition via upregulation of SIRT7 and autophagy pathways."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nPhysical activity further modulates OSTN expression, as evidenced by increased OSTN mRNA levels at the myotendinous junction following eccentric exercise—a finding that suggests a contributory role for OSTN in musculoskeletal adaptation and repair."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Gethin Thomas, Pierre Moffatt, Patrick Salois, et al. 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