Loading...
Effects of cuttlebone powders and their structured calcium compounds against glucocorticoid-induced osteoporosis via MAPK signaling-mediated bone formation
Author(s)
Woonnoi, Wanwipha
Chinfak, Narainrit
Tanasawet, Supita
Saetan, Jirawat
Klaypradit, Wanwimol
Sukketsiri, Wanida
Date Issued
April 1, 2026
Type
Article
Abstract
The effects of dried and calcined cuttlebone powders (DCB and CCB, respectively) and their structured calcium compounds (DCB-OH, DCB-Lac, DCB-CiMa, CCB-OH, CCB-Lac, and CCB-CiMa) on MC3T3-E1 osteoblasts were investigated in vitro . Cytotoxicity analysis using the MTT assay revealed that lower concentrations (10–100 μg/mL) of all compounds were non-toxic, whereas higher concentrations (250–1000 μg/mL) showed dose-dependent cytotoxic effects. Using dexamethasone-induced osteoporosis-like MC3T3-E1 cells, cuttlebone-derived compounds significantly enhanced matrix mineralization as well as alkaline phosphatase (ALP) mRNA expression and activity, indicating restoration of osteoblast function. Additionally, treatment with all cuttlebone compounds reduced dexamethasone-induced apoptosis, demonstrating cytoprotective effects. Gene expression analysis showed suppression of ER stress markers ( CHOP, GRP78, ATF4 ) by most compounds, suggesting attenuation of ER stress-related osteoblast dysfunction. Osteoblast-related genes linked to matrix remodeling and bone formation ( MMP2, MMP9, COL1A1 ) were modulated; treatments generally downregulated MMP2 and upregulated COL1A1 expression. Key osteogenic transcription factors and markers ( BMP4, OC, OSX, RUNX2 ) decreased by dexamethasone were significantly upregulated by cuttlebone compounds, supporting enhanced osteoblast differentiation. Protein phosphorylation studies revealed that these compounds decreased the expression of pERK and p-p38, pathways that are often associated with impaired osteogenesis under glucocorticoid stress. Collectively, these findings demonstrate that cuttlebone powders and their structured calcium compounds mitigate dexamethasone-induced osteoporotic changes in MC3T3-E1 cells by enhancing cell viability, promoting osteoblast differentiation, and reducing apoptosis and ER stress, effects that are associated with suppression of MAPK pathway activation. This finding suggests a possible role in alleviating glucocorticoid-induced dysfunction in MC3T3-E1 osteoblasts and indicates potential relevance for future development as functional food ingredients or nutraceuticals for bone health.
Citation
Journal of Functional Foods, 139, 2026