Low-Intensity Pulsed Ultrasound Affects Chondrocyte Extracellular Matrix Production via an Integrin-Mediated p38 MAPK Signaling Pathway.
Although low-intensity pulsed ultrasound (LIPUS) regulates p38 mitogen-activated protein kinase (MAPK) and promotes cartilage repair in osteoarthritis, the role of integrin-mediated p38 MAPK in the effect of LIPUS on extracellular matrix (ECM) production of normal and OA chondrocytes remains unknown. The aim of this study was to investigate whether LIPUS affects ECM production in normal and OA rabbit chondrocytes through an integrin-p38 signaling pathway. A rabbit model of OA was established by anterior cruciate ligament transection, and chondrocytes were isolated from normal or OA cartilage and cultured in vitro. Chondrocytes were treated with LIPUS and then pre-incubated with the integrin inhibitor GRGDSP or the p38 inhibitor SB203580. Expression of type II collagen, MMP-13, integrin β1, p38 and phosphorylated p38 was assessed by Western blot analysis. We found that type II collagen and integrin β1 were upregulated (p < 0.05), whereas MMP-13 was downregulated (p < 0.05) in normal and OA chondrocytes. Furthermore, phosphorylated p38 was upregulated (p < 0.05) in normal chondrocytes, but downregulated (p < 0.05) in OA chondrocytes after LIPUS stimulation. Pre-incubation of chondrocytes with the integrin inhibitor disrupted the effects of LIPUS on normal and OA chondrocytes. Pre-incubation of chrondocytes with the p38 inhibitor reduced the effects of LIPUS on normal chondrocytes, but had no impact on OA chondrocytes. Our findings suggest that the integrin-p38 MAPK signaling pathway plays an important role in LIPUS-mediated ECM production in chondrocytes.
Department of Rehabilitation Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
Peng
P
Xia
Department of Rehabilitation Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
Shasha
S
Ren
Department of Rehabilitation Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
Qiang
Q
Lin
Department of Rehabilitation Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
Kai
K
Cheng
Department of Rehabilitation Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
Shihao
S
Shen
Department of Rehabilitation Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
Mingxia
M
Gao
Department of Rehabilitation Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China. Electronic address: lixueping6504@163.com.
Xueping
X
Li
D000818:Animals; D015153:Blotting, Western; D002358:Cartilage, Articular / Q000378:metabolism*; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism*; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000378:metabolism*; D016023:Integrins / Q000378:metabolism*; D008297:Male; D010003:Osteoarthritis / Q000378:metabolism; D011817:Rabbits; D015398:Signal Transduction; D000069453:Ultrasonic Waves; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D016023:Integrins; D048051:p38 Mitogen-Activated Protein Kinases
Chondrocytes; Integrin; Low-intensity pulsed ultrasound; Osteoarthritis; p38 MAPK