Role of the SDF-1/CXCR4 signaling pathway in cartilage and subchondral bone in temporomandibular joint osteoarthritis induced by overloaded functional orthopedics in rats.

Abstract

To (i) use a mandibular advancement appliance in rats to investigate the role of the stromal cell-derived factor/CXC receptor 4 (SDF-1/CXCR4) signaling pathway in temporomandibular joint osteoarthritis (TMJ OA) induced by overloaded functional orthopedics (OFO) and (ii) provide a cellular and molecular basis for efficacious treatment of skeletal class-II malocclusion and avoidance of TMJ OA. Male Sprague-Dawley rats (6 weeks) were divided randomly into control + normal saline (NS), EXP + ADM3100 (SDF-1 antagonist), EXP + NS, and control + ADM3100 groups. Changes in articular cartilage and subchondral bone after TMJ OA in these four groups were observed by hematoxylin and eosin (H&E), immunofluorescence double staining (IDS), Safranin-O staining, immunohistochemical (IHC) staining, real-time polymerase chain reaction, and micro-computed tomography at 2, 4, and 8 weeks. OFO led to increased expression of SDF-1, CXCR4, and matrix metalloproteinase (MMP) 13 and decreased expression of collagen II. The thickness of the hypertrophic cartilage layer was reduced at 4 weeks in the EXP + NS group, and damage to subchondral bone was observed at 2 weeks. Using ADM3100 to inhibit SDF-1 signaling could attenuate expression of MMP13, cartilage damage, and osteoblast differentiation. IDS showed that the areas of expression of SDF-1 and OSX in subchondral bone overlapped. Overloaded functional orthopedics (OFO) induced TMJ OA. The destruction of subchondral bone in TMJ OA caused by OFO occurred before damage to cartilage. SDF-1/CXCR4 may induce the osteogenic differentiation and cause cartilage degradation in TMJ OA caused by OFO.