JORT Journal

Abstract

Background: Osteoporosis has been established as a prevalent progressive, age-related chronic inflammatory bone disorders that recognized as global public health concern attributed for its subsequent high risk of mortality and socioeconomic burden. With population aging progression, effective preventive and therapeutic approaches to osteoporosis are urgent. Aloe-emodin (AE) is a bioactive component derived from various Chinese edible medicinal herbs and has diverse health benefits, including anti-inflammatory, anticancer activity and so on. While the accurate efficacy of AE on osteoporosis and its underlying mechanisms remains unveiled. Purpose: The present study aims to investigate the effect of AE on osteoporosis and unravel the underlying mechanisms. Methods: We investigated the efficacy of AE on ovariectomy (OVX) -induced osteoporosis mice model, with micro-CT, bone histomorphometry and immunohistochemistry staining to assess the morphology and molecular changes. In Vitro, ALP and Alizarin Red staining were performed to verify the function of AE on osteoblast differentiation. Moreover, the effects of AE on RANKL-induced osteoclastogenesis were examined utilizing CCK8 assay, TRAP staining and western blot. Furthermore, molecular docking was implied to predict the binding targets of AE during osteoclastogenesis. Results: We demonstrated that AE protects against OVX-induced osteoporosis. In Vitro, AE attenuated osteoclastogenesis by inhibition of RANKL-induced c-Fos/NFATc1 signalling pathway but did not influence osteoblast differentiation. Nevertheless, AE suppressed osteoclast bone resorption and simultaneously enhanced the release of TGF-b1 and IGF-1 to improve osteoblastic bone formation In Vivo. Conclusions: We confirmed that AE can mitigate OVX-induced osteoporosis via suppressing osteoclast formation and meanwhile enhancing TGF-b1 and IGF-1 in the resorption environment. This innovative and exciting discovery pave the way for the application of AE as a natural prevention and treatment agent for osteoporosis.

Keywords: Aloe emodin; Osteoporosis; c-Fos/NFATc1 signalling pathway; Osteoclast; TGF-b1; IGF-1

Abbreviations: AE: Aloe-emodin; ALP: Alkaline Phosphatase; ALT: Alanine Transaminase; AST: Aspartate Aminotransferase; BMDM: Bone Marrow Derived Monocytes; BMSC: Bone Marrow Mesenchyml Stem Cell; BMU: Basic Multicellular Unit; BUN: Blood Urea Nitrogen; BS/TV: Bone Surface vs. Tissue Volume; BV/TV: Trabecular bone volume vs. Tissue volume; CCK-8: Cell counting kit-8, CTSK: Cathepsin K; DMSO: Dimethylsulfoxide; ECM: Extracellular matrix; H&E: Hematoxylin and eosin; I.g: Intragastrically, IGF-1: Insulin-like growth factor-1; IHC: Immunohistochemistry; Micro-CT: Microcomputed tomography; MMPs: Matrix metalloproteinases; NFATc1: Nuclear factor of activated T cells; OPG: Osteoprotegerin; OVX: Ovariectomy; RANKL: Nuclear factor κB receptor activator ligand; Scr: Serum creatinine; TGF-b1: Transforming growth factor -β1; Tb.N.: Trabecular bone number; vs.: Versus.