Oscillating fluid flow activation of gap junction hemichannels induces ATP release from MLO-Y4 osteocytes

被引:238
作者
Genetos, Damian C.
Kephart, Curtis J.
Zhang, Yue
Yellowley, Clare E.
Donahue, Henry J. [1 ]
机构
[1] Penn State Univ, Coll Med, Dept Orthopaed & Rehabil, Div Musculoskeletal Sci, Hershey, PA 17033 USA
[2] Univ Calif Davis, Dept Orthopaed Surg, Sacramento, CA 95817 USA
[3] Univ Calif Davis, Sch Vet Med, Dept Anat Physiol & Cell Biol, Davis, CA 95616 USA
关键词
D O I
10.1002/jcp.21021
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Mechanical loads are required for optimal bone mass. One mechanism whereby mechanical loads are transduced into localized cellular signals is strain-induced fluid flow through lacunae and canaliculi of bone. Gap junctions (GJs) between osteocytes and osteoblasts provides a mechanism whereby flow-induced signals are detected by osteocytes and transduced to osteoblasts. We have demonstrated the importance of GJ and gap junctional intercellular communication (GJIC) in intracellular calcium and prostaglandin E-2 (PGE(2)) increases in response to flow. Unapposed connexons, or hemichannels, are themselves functional and may constitute a novel mechanotransduction mechanism. Using MC3T3-E1 osteoblasts and MLO-Y4 osteocytes, we examined the time course and mechanism of hemichannel activation in response to fluid flow, the composition of the hemichannels, and the role of hemichannels in flow-induced ATP release. We demonstrate that fluid flow activates hemichannels in MLO-Y4, but not MC3T3-E1, through a mechanism involving protein kinase C, which induces ATP and PGE2 release.
引用
收藏
页码:207 / 214
页数:8
相关论文
共 72 条
[11]   Gating and regulation of connexin 43 (U43) hemichannels [J].
Contreras, JE ;
Sáez, JC ;
Bukauskas, FF ;
Bennett, MVL .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (20) :11388-11393
[12]   Metabolic inhibition induces opening of unapposed connexin 43 gap junction hemichannels and reduces gap junctional communication in cortical astrocytes in culture [J].
Contreras, JE ;
Sánchez, HA ;
Eugenin, EA ;
Speidel, D ;
Theis, M ;
Willecke, K ;
Bukauskas, FF ;
Bennett, MVL ;
Sáez, JC .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (01) :495-500
[13]   CANDIDATES FOR THE MECHANOSENSORY SYSTEM IN BONE [J].
COWIN, SC ;
MOSSSALENTIJN, L ;
MOSS, ML .
JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME, 1991, 113 (02) :191-197
[14]   PTHrP signaling targets cyclin D1 and induces osteoblastic cell growth arrest [J].
Datta, NS ;
Chen, C ;
Berry, JE ;
McCauley, LK .
JOURNAL OF BONE AND MINERAL RESEARCH, 2005, 20 (06) :1051-1064
[15]  
DAVIDSON JS, 1988, J PHARMACOL EXP THER, V246, P1104
[16]   REVERSIBLE INHIBITION OF INTERCELLULAR JUNCTIONAL COMMUNICATION BY GLYCYRRHETINIC ACID [J].
DAVIDSON, JS ;
BAUMGARTEN, IM ;
HARLEY, EH .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1986, 134 (01) :29-36
[17]   Receptor-mediated facilitation of cell volume regulation by swelling-induced ATP release in human epithelial cells [J].
Dezaki, K ;
Tsumura, T ;
Maeno, E ;
Okada, Y .
JAPANESE JOURNAL OF PHYSIOLOGY, 2000, 50 (02) :235-241
[18]   Gap junctions and biophysical regulation of bone cell differentiation [J].
Donahue, HJ .
BONE, 2000, 26 (05) :417-422
[19]   MORPHOLOGICAL EVIDENCE OF GAP-JUNCTIONS BETWEEN BONE-CELLS [J].
DOTY, SB .
CALCIFIED TISSUE INTERNATIONAL, 1981, 33 (05) :509-512
[20]   MECHANOTRANSDUCTION AND THE FUNCTIONAL-RESPONSE OF BONE TO MECHANICAL STRAIN [J].
DUNCAN, RL ;
TURNER, CH .
CALCIFIED TISSUE INTERNATIONAL, 1995, 57 (05) :344-358