MMP14 Silencing Alleviates Inflammation‐Associated Bone Loss in Chronic Periodontitis and Postmenopausal Osteoporosis in Association With Reduced JAK2 / STAT3 Signaling

Chronic periodontitis (CP) and postmenopausal osteoporosis (PMOP) are prevalent chronic inflammatory diseases characterized by bone resorption; however, the shared molecular mechanisms between them remain unclear. Hub genes associated with CP and PMOP were identified through bioinformatics analysis. Lipopolysaccharide (LPS)-stimulated MC3T3-E1 osteoblasts were used to establish an in vitro model, followed by lentiviral-mediated matrix metalloproteinase 14 (MMP14) knockdown. Cell viability and apoptosis were assessed using the Cell Counting Kit-8 assay and flow cytometry, respectively. Levels of inflammatory cytokines and oxidative stress markers were measured by enzyme-linked immunosorbent assay. Intracellular ROS were detected using 2',7'-dichlorodihydrofluorescein diacetate fluorescence staining. Western blot analysis was performed to assess the expression of osteoclast-related markers. The involvement of the JAK2/STAT3 pathway was assessed using the JAK2 agonist RO8191 and inhibitor AG490. PDGFRB, MMP14, VWF, PECAM1, FLT1, and CXCR4 were identified as hub genes and were all upregulated in LPS-stimulated MC3T3-E1 osteoblasts. Silencing MMP14 improved cell viability and reduced apoptosis, inflammatory cytokine release (TNF-α, IL-1β, and IL-6), oxidative stress markers (MDA and ROS), and osteoclast-associated markers (CTX-I, TRAP, and Cathepsin K), while restoring SOD activity. Mechanistically, MMP14 silencing decreased the phosphorylation levels of JAK2 and STAT3. The protective phenotype caused by MMP14 silencing was significantly abolished by RO8191 but mimicked by treatment with AG490. MMP14 may represent a potential molecular link between CP-associated bone loss and PMOP. Modulation of the MMP14-JAK2/STAT3 signaling axis may represent a promising research direction for inflammation-related bone loss.