Abstract
Mandibular hypoplasia is a common jaw deformity that affects breathing, occlusal function and facial aesthetics. Stimulating mandibular condylar growing with functional appliances is an ordinary but controversial treatment method in orthodontics. Therefore, it is vital to clarify how functional appliances affect condylar growing. Raf-1 kinase inhibitor protein (RKIP), as an endogenous inhibitory molecule of the ERK signaling, is postulated to involve in stress-induced response to articular cartilage. This study was to reveal the role of RKIP in regulating cartilage matrix synthesis with functional appliance treatment. Here, position rat mandibular forward simulating functional appliance effect to examine the stress-induced modification of mandibular condylar in vivo, meanwhile rat mandibular condylar chondrocytes (Mccs) were subjected to cyclic tensile stress (CTS, 16%, 1 HZ). The results showed that mandibular forward therapy enhanced condylar cartilage growth. The thicknesses of all layers of condylar cartilage were increased significantly. RKIP expression was also increased in the mature cartilage layer. In addition, CTS could enhance extracellular matrix formation and cartilage marker expression (aggrecan and collagen II), which shared a similar expression pattern with RKIP in Mccs. However, CTS induced up-regulation of collagen II and aggrecan was blocked by RKIP knockdown. Nuclear p-ERK, targeting downstream of RKIP, showed a decrease after CTS,which was disappeared in RKIP-knockdown Mccs. Taken together, physiological mechanical stimulation promotes cartilage growth modification by up-regulating RKIP through inhibiting ERK signaling pathway.
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Acknowledgements
This research is supported by the National Key Clinical Specialist Construction Programs of China,Natural Science Foundation of Jiangsu Province, China (BK20150999), and Natural science fund for colleges and universities in Jiangsu Province, China (15KJB320004). We thank the Jiangsu Key Laboratory of Oral Diseases from the Stomatology Collage of Nanjing Medical University for providing experimental equipment.
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Conceived and designed the experiments: LW, WBZ. Performed the experiments: LS, JZ. Analyzed the data: HW. Contributed reagents/materials/analysis tools: YP. Wrote the paper: LS.
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Lian Sun and Jing Zhao contributed equally to this work. All authors declare that there are not any financial and personal relationships with other people or organizations that could potentially and inappropriately influence (bias) their work and conclusions.
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Lian Sun and Jing Zhao have contributed equally to this work.
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10735_2017_9741_MOESM1_ESM.eps
Supplement 1 Forward mandibular positioning rat model. Mental tube with a 135 degree angle leaned to labial side was bonded to lower incisors to simulate functional appliance effect (S1 a). X-ray was used to exam sagittal and vertical opening lengths of mandibular(S1 b). (EPS 16641 KB)
10735_2017_9741_MOESM2_ESM.eps
Supplement 2 Identification of mandibular condylar chondrocytes (Mccs). The morphology of the P2 chondrocytes was observed under a microscope (S2 a). The alcian blue staining was positive in the chondrocytes (S2 b). The immunofluorescence staining for type II collagen was positive in the chondrocytes (S2 c). (EPS 21450 KB)
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Sun, L., Zhao, J., Wang, H. et al. Mechanical stress promotes matrix synthesis of mandibular condylar cartilage via the RKIP-ERK pathway. J Mol Hist 48, 437–446 (2017). https://doi.org/10.1007/s10735-017-9741-4
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DOI: https://doi.org/10.1007/s10735-017-9741-4