Temporal gradients in shear stimulate osteoblastic proliferation via ERK1/2 and retinoblastoma protein

American Journal of Physiology - Endocrinology and Metabolism - Tập 283 Số 2 - Trang E383-E389 - 2002
Guangliang Jiang1, Charles R. White1, Hazel Y. Stevens1, John A. Frangos1
1Department of Bioengineering, University of California, San Diego, La Jolla, California 92093

Tóm tắt

Bone cells are subject to interstitial fluid flow (IFF) driven by venous pressure and mechanical loading. Rapid dynamic changes in mechanical loading cause transient gradients in IFF. The effects of pulsatile flow (temporal gradients in fluid shear) on rat UMR106 cells and rat primary osteoblastic cells were studied. Pulsatile flow induced a 95% increase in S-phase UMR106 cells compared with static controls. In contrast, ramped steady flow stimulated only a 3% increase. Similar patterns of S-phase induction were also observed in rat primary osteoblastic cells. Pulsatile flow significantly increased relative UMR106 cell number by 37 and 62% at 1.5 and 24 h, respectively. Pulsatile flow also significantly increased extracellular signal-regulated kinase (ERK1/2) phosphorylation by 418%, whereas ramped steady flow reduced ERK1/2 activation to 17% of control. Correspondingly, retinoblastoma protein was significantly phosphorylated by pulsatile fluid flow. Inhibition of mitogen-activated protein (MAP)/ERK kinase (MEK)1/2 by U0126 (a specific MEK1/2 inhibitor) reduced shear-induced ERK1/2 phosphorylation and cell proliferation. These findings suggest that temporal gradients in fluid shear stress are potent stimuli of bone cell proliferation.

Từ khóa


Tài liệu tham khảo

10.1074/jbc.270.40.23589

10.1152/ajpheart.2000.278.5.H1598

10.1091/mbc.2.12.965

Fribourg AF, 2000, Cell Growth Differ, 11, 361

10.1074/jbc.M008867200

10.1074/jbc.274.31.22033

10.1115/1.1389460

10.1074/jbc.M002766200

10.1002/bit.260430706

10.1007/s002239900185

10.1152/ajpheart.1999.277.4.H1593

Hung CT, 1995, Clin Orthop, 313, 256

10.1016/0021-9290(96)84535-0

10.1016/0092-8674(92)90162-6

10.1016/S0021-9290(98)00114-6

10.1152/ajpendo.1996.271.1.E205

10.1016/0955-0674(94)90141-4

10.1016/S0960-9822(95)00151-5

10.1042/bj3570297

10.1006/mvre.1999.2215

10.1359/jbmr.1999.14.6.930

10.1016/0026-2862(88)90084-2

Nillson BE., 1971, Clin Orthop Rel Res, 77, 179

Noble B, 1999, Horm Res, 51, 31

10.1016/S0898-6568(99)00071-6

10.1002/1097-0142(20010315)91:6<1156::AID-CNCR1112>3.0.CO;2-1

10.1002/jor.1100080115

10.1038/269080a0

Qin YX, 2000, Trans Ortho Res Soc, 25, 740

10.1002/jcp.1041430113

10.1152/ajpcell.1991.261.3.C428

10.1007/BF00675628

10.1210/endo.138.3.4999

10.1152/jappl.1990.68.1.13

10.1073/pnas.93.2.679

10.1074/jbc.270.16.9420

10.1016/S1350-4533(00)00017-5

10.1016/8756-3282(95)00100-R

10.1046/j.1469-7580.2000.19620181.x

10.1016/S1350-4533(00)00021-7

10.1016/0021-9290(94)90010-8

10.1007/BF02406148

10.1161/01.CIR.103.20.2508

10.1152/physrev.1999.79.1.143

10.1016/S0898-6568(01)00185-1

10.1073/pnas.96.20.11335