Hydrostatic Compress Force Enhances the Viability and Decreases the Apoptosis of Condylar Chondrocytes through Integrin-FAK-ERK/PI3K Pathway.
Reduced mechanical stimuli in many pathological cases, such as hemimastication and limited masticatory movements, can significantly affect the metabolic activity of mandibular condylar chondrocytes and the growth of mandibles. However, the molecular mechanisms for these phenomena remain unclear. In this study, we hypothesized that integrin-focal adhesion kinase (FAK)-ERK (extracellular signal-regulated kinase)/PI3K (phosphatidylinositol-3-kinase) signaling pathway mediated the cellular response of condylar chondrocytes to mechanical loading. Primary condylar chondrocytes were exposed to hydrostatic compressive forces (HCFs) of different magnitudes (0, 50, 100, 150, 200, and 250 kPa) for 2 h. We measured the viability, morphology, and apoptosis of the chondrocytes with different treatments as well as the gene, protein expression, and phosphorylation of mechanosensitivity-related molecules, such as integrin α2, integrin α5, integrin β1, FAK, ERK, and PI3K. HCFs could significantly increase the viability and surface area of condylar chondrocytes and decrease their apoptosis in a dose-dependent manner. HCF of 250 kPa resulted in a 1.51 ± 0.02-fold increase of cell viability and reduced the ratio of apoptotic cells from 18.10% ± 0.56% to 7.30% ± 1.43%. HCFs could significantly enhance the mRNA and protein expression of integrin α2, integrin α5, and integrin β1 in a dose-dependent manner, but not ERK1, ERK2, or PI3K. Instead, HCF could significantly increase phosphorylation levels of FAK, ERK1/2, and PI3K in a dose-dependent manner. Cilengitide, the potent integrin inhibitor, could dose-dependently block such effects of HCFs. HCFs enhances the viability and decreases the apoptosis of condylar chondrocytes through the integrin-FAK-ERK/PI3K pathway.
School of Stomatology, Zhejiang Chinese Medical University, Hangzhou 310053, China. whiterose1989@126.com.|Department of Oral Implantology and Prosthetic Dentistry, Academic Centre for Dentistry Amsterdam (ACTA), VU University Amsterdam and University of Amsterdam, MOVE Research Institute, Gustav Mahlerlaan 3004, Amsterdam 1081LA, Nord-Holland, The Netherlands. whiterose1989@126.com.
Dandan
D
Ma
Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing 100081, China. kouxiaoxing@gmail.com.
Xiaoxing
X
Kou
School of Stomatology, Zhejiang Chinese Medical University, Hangzhou 310053, China. jinjingtoday@163.com.
Jing
J
Jin
Department of Orthopaedic Surgery, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, China. nacle1990829@163.com.
Taotao
T
Xu
Department of Orthodontics, Stomatology Hospital Affiliated to Zhejiang University, Hangzhou 310053, China. baobalala@sina.cn.
Mengjie
M
Wu
School of Stomatology, Zhejiang Chinese Medical University, Hangzhou 310053, China. totti.12345@163.com.
Liquan
L
Deng
School of Stomatology, Zhejiang Chinese Medical University, Hangzhou 310053, China. fulusi@126.com.
Lusi
L
Fu
Department of Oral Implantology and Prosthetic Dentistry, Academic Centre for Dentistry Amsterdam (ACTA), VU University Amsterdam and University of Amsterdam, MOVE Research Institute, Gustav Mahlerlaan 3004, Amsterdam 1081LA, Nord-Holland, The Netherlands. liuzzd@163.com.
Yi
Y
Liu
Department of Oral Implantology and Prosthetic Dentistry, Academic Centre for Dentistry Amsterdam (ACTA), VU University Amsterdam and University of Amsterdam, MOVE Research Institute, Gustav Mahlerlaan 3004, Amsterdam 1081LA, Nord-Holland, The Netherlands. g.wu@acta.nl.
Gang
G
Wu
School of Stomatology, Zhejiang Chinese Medical University, Hangzhou 310053, China. haipinglushu@hotmail.com.
Haiping
H
Lu
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D058543:Class Ia Phosphatidylinositol 3-Kinase / Q000235:genetics / Q000378:metabolism; D019245:Compressive Strength / Q000502:physiology; D051417:Focal Adhesion Kinase 1 / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006874:Hydrostatic Pressure; D039421:Integrin alpha2 / Q000235:genetics / Q000378:metabolism*; D039482:Integrin alpha5 / Q000235:genetics / Q000378:metabolism; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism; D008335:Mandibular Condyle / Q000166:cytology / Q000378:metabolism; D040542:Mechanotransduction, Cellular; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism*; D061251:Primary Cell Culture; D051381:Rats; D017207:Rats, Sprague-Dawley; D012910:Snake Venoms / Q000494:pharmacology
D039421:Integrin alpha2; D039482:Integrin alpha5; D019012:Integrin beta1; D012910:Snake Venoms; C422910:Cilengitide; D058543:Class Ia Phosphatidylinositol 3-Kinase; D051417:Focal Adhesion Kinase 1; C496052:Ptk2 protein, rat; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
ERK; FAK; PI3K; apoptosis; chondrocyte; integrin; mandibular condyle