Mechanotransduction in stretched osteocytes: temporal expression of immediate early and other genes

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Kawata, Akira¹; Mikuni-Takagaki, Yuko¹

Mechanotransduction in stretched osteocytes: temporal expression of immediate early and other genes

Biochem Biophys Res Commun. May 19, 1998;246(2):404-408

©1998 Academic Press.

Affiliations

¹Departments of Oral Biochemistry, Kanagawa Dental College, Yokosuka, 238-8580, Japan
Abstract

Osteocytes, dendritic bone cells, transduce signals of mechanical loading that results in bone formation. We have reported in stretched primary osteocytes that the cAMP level, IGF-I and osteocalcin protein levels were elevated (Endocrinology 137:2028, 1996). Here we report that stretching induces the expression of immediate early genes, c-fos and COX-2; inducive cyclooxygenase gene. Compared to c-fos, COX-2 as well as IGF-I and osteocalcin mRNA appeared in a biphasic manner; second peaks at 8 (COX-2) or 24 hrs (IGF-I and osteocalcin) later. Furthermore, these second peaks are abolished by including NS398, a specific inhibitor of the inducive cyclooxygenase, during the 3-hr stretching. A sequence that the calcium influx activates PkA which, in turn, activates c-fos and COX-2 transcription resulting in the production of proteins such as IGF-I and osteocalcin. A long-lasting effect of mechanical loadingin vivocan be explained from the secondary anabolic reaction we observed through the upregulated COX-2 mRNA.
Links

DOI: 10.1006/bbrc.1998.8632

PubMed: 9610372

WoS: 000073796900020
History

Received: 1998-04-1

Cited Works (7)

Year	Entry
1995	Lean JM, Jagger CJ, Chambers TJ, Chow JWM. Increased insulin-like growth factor I mRNA expression in rat osteocytes in response to mechanical stimulation. Am J Physiol Endocrinol Metab. February 1995;268(1):E318-E327.
1996	Lean JM, Mackay AG, Chow JW, Chambers TJ. Osteocytic expression of mRNA for c-fos and IGF-I: an immediate early gene response to an osteogenic stimulus. Am J Physiol Endocrinol Metab. June 1996;270(6):E937-E945.
1995	Klein-Nulend J, van der Plas A, Semeins CM, Ajubi NE, Frangos JA, Nijweide PJ, Burger EH. Sensitivity of osteocytes to biomechanical stress in vitro. FASEB J. March 1995;9(5):441-445.
1994	Turner CH, Forwood MR, Otter MW. Mechanotransduction in bone: do bone cells act as sensors of fluid flow? FASEB J. August 1994;8(11):875-878.
1996	Mikuni-Takagaki Y, Suzuki Y, Kawase T, Saito S. Distinct responses of different populations of bone cells to mechanical stress. Endocrinology. May 1996;137(5):2028-2035.
1995	Klein-Nulend J, Semeins CM, Ajubi NE, Nijweide P, Burger EH. Pulsating fluid flow increases nitric oxide (NO) synthesis by osteocytes but not periosteal fibroblasts - correlation with prostaglandin upregulation. Biochem Biophys Res Commun. December 14, 1995;217(2):640-648.
1991	Rawlinson SCF, El‐Haj AJ, Minter SL, Tavares IA, Bennett A, Lanyon LE. Loading‐related increases in prostaglandin production in cores of adult canine cancellous bone in vitro: a role for prostacyclin in adaptive bone remodeling? J Bone Miner Res. December 1991;6(12):1345-1351.

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2001	Young MF, Dieudonné SC. Molecular biology techniques to measure skeletal gene expression. In: Cowin SC, ed. Bone Mechanics Handbook. 2nd ed. Boca Raton, FL: CRC Press; 2001:3-1–.
2003	Noble BS, Peet N, Stevens HY, Brabbs A, Mosley JR, Reilly GC, Reeve J, Skerry TM, Lanyon LE. Mechanical loading: biphasic osteocyte survival and targeting of osteoclasts for bone destruction in rat cortical bone. Am J Physiol Cell Physiol. April 2003;284(4):C934-C943.
2021	Smit TH. Closing the osteon: do osteocytes sense strain rate rather than fluid flow? BioEssays. August 2021;43(8):2000327.
2003	Simmons CA, Matlis S, Thornton AJ, Chen S, Wang C-Y, Mooney DJ. Cyclic strain enhances matrix mineralization by adult human mesenchymal stem cells via the extracellular signal-regulated kinase (ERK1/2) signaling pathway. J Biomech. August 2003;36(8):1087-1096.
2004	Mullender M, El Haj AJ, Yang Y, van Duin MA, Burger EH, Klein-Nulend J. Mechanotransduction of bone cells in vitro: mechanobiology of bone tissue. Med Biol Eng Comput. January 2004;42(1):14-21.
2002	Ehrlich PJ, Lanyon LE. Mechanical strain and bone cell function: a review. Osteoporos Int. September 2002;13(9):688-700.
2015	Scully N. Differentiation of Osteoblasts to Osteocytes in 3D Type I Collagen Gels: A Novel Tool to Study Osteocyte Responses to Mechanical Loading [PhD thesis]. Cardiff, UK: Cardiff University; April 2015.
2005	Takai E. Modulation of Bone Cell Mechanotransduction [PhD thesis]. Columbia University; 2005.
2009	Chan M. Mechanobiology of 3D Co-Culture Trabecular Explant Model [PhD thesis]. Columbia University; 2009.
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2016	Druchok C. Temporal Influence of NSAIDs on Mechanically Induced Bone Formation and Fluid Flow Stimulated Cellular PGE₂ Production [PhD thesis]. Hamilton, ON: McMaster University; August 2016.
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2017	Morse AR. The Role of Wnt/β-Catenin Antagonists - Sclerostin and DKK1 - in Bone Homeostasis and Mechanotransduction [PhD thesis]. University of Sydney; 2017.
2005	McGarry JG. Computational and Experimental Investigation of Bone Cell Response to Mechanical Stimuli [PhD thesis]. Trinity College Dublin; September 2005.
2003	Youn I. Osteogenic Properties of the Periosteum: In Vitro Characterizations and Its Potential Application to Bone-Tunnel Healing [PhD thesis]. Tulane University; 2003.
1999	Judex S. The Effect of Exercise-Induced Mechanical Stimuli on Cortical Bone [PhD thesis]. Calgary, AB: University of Calgary; 1999.
2020	Pei S. Osteocyte Mechanosensing: Interstitial Fluid Flow, Cellular Response, and Turnover of Pericellular Matrix [PhD thesis]. University of Delaware; 2020.
2003	Ominsky MS. Effects of Hydrostatic Pressure, Biaxial Strain, and Fluid Shear on Osteoblastic Cells: Mechanotransduction Via NF-ΚB, MAP Kinase, and AP-1 Pathways [PhD thesis]. University of Michigan; 2003.
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2009	Rath AL. The Effects of Strain and Perilacunar Environment on the Mechanotransduction of Osteocytes [PhD thesis]. Winston-Salem, NC: Wake Forest University; May 2009.
2007	Christiansen BA. Vibrational Stimulation of Bone Formation in Mice [PhD thesis]. St. Louis, MO: Washington University in St. Louis; December 2007.