title: A Trabecular Bone Explant Model of Osteocyte-Osteoblast Co-Culture for Bone Mechanobiology.
abstract: The osteocyte network is recognized as the major mechanical sensor in the bone remodeling process, and osteocyte-osteoblast communication acts as an important mediator in the coordination of bone formation and turnover. In this study, we developed a novel 3D trabecular bone explant co-culture model that allows live osteocytes situated in their native extracellular matrix environment to be interconnected with seeded osteoblasts on the bone surface. Using a low-level medium perfusion system, the viability of in situ osteocytes in bone explants was maintained for up to 4 weeks, and functional gap junction intercellular communication (GJIC) was successfully established between osteocytes and seeded primary osteoblasts. Using this novel co-culture model, the effects of dynamic deformational loading, GJIC, and prostaglandin E(2) (PGE(2)) release on functional bone adaptation were further investigated. The results showed that dynamical deformational loading can significantly increase the PGE(2) release by bone cells, bone formation, and the apparent elastic modulus of bone explants. However, the inhibition of gap junctions or the PGE(2) pathway dramatically attenuated the effects of mechanical loading. This 3D trabecular bone explant co-culture model has great potential to fill in the critical gap in knowledge regarding the role of osteocytes as a mechano-sensor and how osteocytes transmit signals to regulate osteoblasts function and skeletal integrity as reflected in its mechanical properties.
authors.affiliation: Bone Bioengineering Laboratory, Department of Biomedical Engineering, Columbia University, 351 Engineering Terrace, Mail Code 8904, 1210 Amsterdam Avenue, New York, NY 10027, USA.
authors.forename: Meilin Ete
authors.initials: ME
authors.lastname: Chan
authors.forename: Xin L
authors.initials: XL
authors.lastname: Lu
authors.forename: Bo
authors.initials: B
authors.lastname: Huo
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Baik
authors.forename: Victor
authors.initials: V
authors.lastname: Chiang
authors.forename: Robert E
authors.initials: RE
authors.lastname: Guldberg
authors.forename: Helen H
authors.initials: HH
authors.lastname: Lu
authors.forename: X Edward
authors.initials: XE
authors.lastname: Guo
references.citation: J Bone Miner Res. 2000 Feb;15(2):209-17
references.pmid: 10703922
references.citation: Mol Biol Cell. 2005 Jul;16(7):3100-6
references.pmid: 15843434
references.citation: J Biomech. 1991;24 Suppl 1:101-9
references.pmid: 1791171
references.citation: J Musculoskelet Neuronal Interact. 2006 Oct-Dec;6(4):408-17
references.pmid: 17185839
references.citation: Tissue Eng. 2003 Dec;9(6):1197-203
references.pmid: 14670107
references.citation: Tissue Eng Part A. 2008 Jan;14(1):117-26
references.pmid: 18333810
references.citation: J Biomech. 2001 May;34(5):671-7
references.pmid: 11311708
references.citation: J Biol Chem. 2008 Sep 26;283(39):26374-82
references.pmid: 18676366
references.citation: J Bone Miner Res. 2002 Jun;17(6):1015-25
references.pmid: 12054156
references.citation: J Biomech. 1998 Nov;31(11):969-76
references.pmid: 9880053
references.citation: FASEB J. 1995 Dec;9(15):1614-22
references.pmid: 8529841
references.citation: J Bone Miner Res. 1990 Sep;5(9):923-32
references.pmid: 1704173
references.citation: Exerc Sport Sci Rev. 2000 Oct;28(4):185-8
references.pmid: 11064853
references.citation: Bone. 2008 May;42(5):837-40
references.pmid: 18295563
references.citation: J Biomech. 1996 Nov;29(11):1411-7
references.pmid: 8894921
references.citation: Proc Natl Acad Sci U S A. 2007 Aug 14;104(33):13325-30
references.pmid: 17673554
references.citation: Bone. 2000 Aug;27(2):241-7
references.pmid: 10913917
references.citation: Am J Physiol Cell Physiol. 2007 Jan;292(1):C545-52
references.pmid: 16885390
references.citation: J Appl Physiol (1985). 2001 May;90(5):1849-54
references.pmid: 11299276
references.citation: J Bone Miner Res. 1991 Dec;6(12):1345-51
references.pmid: 1724342
references.citation: J Bone Miner Res. 2006 Feb;21(2):183-92
references.pmid: 16418774
references.citation: FASEB J. 1999;13 Suppl:S101-12
references.pmid: 10352151
references.citation: Front Biosci. 2007 Jan 01;12:1450-62
references.pmid: 17127393
references.citation: Biochem Biophys Res Commun. 1996 Aug 5;225(1):62-8
references.pmid: 8769095
references.citation: J Appl Physiol (1985). 2004 Mar;96(3):957-66
references.pmid: 14617531
references.citation: Eur Cell Mater. 2006 Apr 12;11:57-75; discussion 75
references.pmid: 16612792
references.citation: Bone. 2003 Jul;33(1):64-70
references.pmid: 12919700
references.citation: Osteoarthritis Cartilage. 1999 Jul;7(4):422-3
references.pmid: 10419787
references.citation: J Cell Physiol. 2007 Jul;212(1):207-14
references.pmid: 17301958
references.citation: J Bone Miner Res. 1993 Mar;8(3):251-9
references.pmid: 7681245
references.citation: Biochem Biophys Res Commun. 2003 Jun 6;305(3):677-83
references.pmid: 12763047
references.citation: J Orthop Res. 2006 Aug;24(8):1687-98
references.pmid: 16788985
references.citation: J Dent Res. 2006 Oct;85(10):905-9
references.pmid: 16998129
references.citation: Proc Natl Acad Sci U S A. 2002 Oct 1;99(20):12600-5
references.pmid: 12242339
references.citation: Tissue Eng. 2005 Nov-Dec;11(11-12):1832-9
references.pmid: 16411829
references.citation: Adv Exp Med Biol. 1997;433:295-8
references.pmid: 9561155
references.citation: J Bone Miner Res. 2004 Sep;19(9):1403-10
references.pmid: 15312240
references.citation: Calcif Tissue Int. 1992 Aug;51(2):132-6
references.pmid: 1422952
references.citation: Am J Physiol Endocrinol Metab. 2003 Sep;285(3):E608-13
references.pmid: 12746215
references.citation: Cell Metab. 2007 Jun;5(6):464-75
references.pmid: 17550781