Low-intensity pulsed ultrasound (LIPUS) induces RANKL, MCP-1, and MIP-1beta expression in osteoblasts through the angiotensin II type 1 receptor.
Constant mechanical stress is essential for the maintenance of bone mass and strength, which is achieved through the cooperative functions of osteoblasts and osteoclasts. However, it has not been fully elucidated how these cell types mediate mechanical signals. Low-intensity pulsed ultrasound (LIPUS) therapy is a recently developed method for application of mechanical stress, and is used clinically to promote bone fracture healing. In the present study, we applied LIPUS to osteoblasts at different stages of maturation and analyzed their chemokine and cytokine expression. In comparison with their immature counterparts, mature osteoblasts expressed significantly higher levels of mRNAs for the receptor activator of nuclear factor kappa B ligand (RANKL), monocyte chemoattractant protein (MCP)-1, and macrophage-inflammatory protein (MIP)-1beta after a few hours of LIPUS treatment. Intriguingly, protein and mRNA expression of angiotensin II type 1 receptor (AT1), a known mechanoreceptor in cardiomyocytes, was detected in osteoblasts, and the level of expression increased significantly during cell maturation. Furthermore, LIPUS-induced extracellular signal-regulated kinase (ERK) phosphorylation and RANKL/chemokine expression was abrogated by a specific AT1 inhibitor. Thus, AT1 may play one of the essential roles in bone metabolism as a mechanoreceptor of osteoblasts.
Bandow
Kenjiro
K
Department of Biochemistry and Molecular Dentistry, Field of Developmental Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
Nishikawa
Yoshiaki
Y
Ohnishi
Tomokazu
T
Kakimoto
Kyoko
K
Soejima
Kazuhisa
K
Iwabuchi
Sadahiro
S
Kuroe
Kazuto
K
Matsuguchi
Tetsuya
T
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds; D002454:Cell Differentiation; D018932:Chemokine CCL2 / Q000096:biosynthesis* / Q000235:genetics; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000235:genetics / Q000378:metabolism; D019742:Chemokines, CC / Q000096:biosynthesis* / Q000235:genetics; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D040542:Mechanotransduction, Cellular; D051379:Mice; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D053244:Osteoprotegerin / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D053245:RANK Ligand / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D044140:Receptor, Angiotensin, Type 1 / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics; D013314:Stress, Mechanical; D013777:Tetrazoles / Q000494:pharmacology; D013997:Time Factors; D014464:Ultrasonic Therapy / Q000379:methods; D015854:Up-Regulation
D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; C491768:Ccl2 protein, mouse; C496535:Ccl4 protein, mouse; D018932:Chemokine CCL2; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D019742:Chemokines, CC; D053244:Osteoprotegerin; D053245:RANK Ligand; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; C506031:Tnfrsf11b protein, mouse; C505689:Tnfsf11 protein, mouse; D048049:Extracellular Signal-Regulated MAP Kinases; C081643:candesartan