Recent Advances in Clinical Trials
Open AccessLow-dose Dexamethasone Primes the IGF-1 Receptor to Enhance Osteoblast Proliferation and Mineralization: A Mechanistic Strategy for Hepatic Osteodystrophy
Authors: Chi-Ming Chiang.
Abstract
Background: Hepatic osteodystrophy (HOD) compromises skeletal integrity and fracture healing in chronic liver disease through defects in vitamin D metabolism, calcium–phosphate homeostasis, and reduced endocrine insulin-like growth factor-1 (IGF-1) output. In surgical settings, glucocorticoids are commonly used for perioperative inflammation control, yet their dose-dependent effects on osteoblasts remain controversial, particularly in the context of HOD. We investigated whether clinically relevant low-dose dexamethasone (Dex) enhances osteoblast proliferation and matrix mineralization by upregulating the insulin-like growth factor-1 receptor (IGF-1R), thereby potentially enhancing cellular responsiveness to limited systemic or local IGF-1.
Methods: Human (hFOB1.19) and murine (7F2) osteoblasts were treated with calcitriol and Dex across a broad concentration range. Cell viability (MTT), proliferation markers (Ki-67, PCNA), receptor signaling (vitamin D receptor [VDR], glucocorticoid receptor [GR]/phosphorylated GR [p-GR], IGF-1R), osteogenic effectors (type I collagen, osteocalcin), and Alizarin Red S–detectable mineralization were quantified by qPCR, immunoblotting, and histochemical staining.
Results: Calcitriol increased osteoblast viability, whereas Dex exhibited a biphasic response: 1–10 nM enhanced viability, whereas ≥100 nM abrogated the low-dose increase and returned values toward baseline in both hFOB1.19 and 7F2 cells. Within this low-dose window, Dex increased Ki-67 and PCNA and—most notably—upregulated IGF-1R mRNA and protein after 48 h. Dex also modulated VDR and GR signaling, increased type I collagen and osteocalcin expression, and accelerated mineral deposition over 7–28 days, with mineralization patterns comparable to calcitriol.
Conclusions: Low-dose Dex reprograms osteoblasts toward proliferation and mineralization and elevates IGF-1R abundance, plausibly amplifying responsiveness to endocrine and paracrine IGF-1. These data support a testable perioperative strategy for HOD: vitamin D3 repletion paired with carefully titrated low-dose Dex to potentially enhance osteoblast IGF-1 responsiveness via IGF-1R upregulation while minimizing glucocorticoid toxicity.
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