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Published in: Calcified Tissue International 1/2015

01-01-2015 | Original Research

Primary Cilia Exist in a Small Fraction of Cells in Trabecular Bone and Marrow

Authors: Thomas R. Coughlin, Muriel Voisin, Mitchell B. Schaffler, Glen L. Niebur, Laoise M. McNamara

Published in: Calcified Tissue International | Issue 1/2015

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Abstract

Primary cilia are potent mechanical and chemical sensory organelles in cells of bone lineage in tissue culture. Cell culture experiments suggest that primary cilia sense fluid flow and this stimulus is translated through biochemical signaling into an osteogenic response in bone cells. Moreover, in vivo, primary cilia knockout in bone cells attenuates bone formation in response to loading. However, understanding the role of the primary cilium in bone mechanotransduction requires knowledge of its incidence and location in vivo. We used immunohistochemistry to quantify the number of cells with primary cilia within the trabecular bone tissue and the enclosed marrow of ovine cervical vertebrae. Primary cilia were identified in osteocytes, bone lining cells, and in cells within the marrow, but were present in only a small fraction of cells. Approximately 4 % of osteocytes and 4.6 % of bone lining cells expressed primary cilia. Within the marrow space, only approximately 1 % of cells presented primary cilia. The low incidence of primary cilia may indicate that cilia either function as mechanosensors in a selected number of cells, function in concert with other mechanosensing mechanisms, or that the role of primary cilia in mechanosensing is secondary to its role in chemosensing or cellular attachment.
Literature
1.
2.
go back to reference Gurkan UA, Akkus O (2008) The mechanical environment of bone marrow: a review. Ann Biomed Eng 36:1978–1991CrossRefPubMed Gurkan UA, Akkus O (2008) The mechanical environment of bone marrow: a review. Ann Biomed Eng 36:1978–1991CrossRefPubMed
3.
go back to reference Weiss L (1976) The hematopoietic microenvironment of the bone marrow: an ultrastructural study of the stroma in rats. Anat Rec 186:161–184CrossRefPubMed Weiss L (1976) The hematopoietic microenvironment of the bone marrow: an ultrastructural study of the stroma in rats. Anat Rec 186:161–184CrossRefPubMed
4.
go back to reference Birmingham E, Grogan JA, Niebur GL, McNamara LM, McHugh PE (2013) Computational modelling of the mechanics of trabecular bone and marrow using fluid structure interaction techniques. Ann Biomed Eng 41:814–826CrossRefPubMed Birmingham E, Grogan JA, Niebur GL, McNamara LM, McHugh PE (2013) Computational modelling of the mechanics of trabecular bone and marrow using fluid structure interaction techniques. Ann Biomed Eng 41:814–826CrossRefPubMed
5.
go back to reference Birmingham E, Niebur GL, McHugh PE, Shaw G, Barry FP, McNamara LM (2012) Osteogenic differentiation of mesenchymal stem cells is regulated by osteocyte and osteoblast cells in a simplified bone niche. Eur Cell Mater 23:13–27PubMed Birmingham E, Niebur GL, McHugh PE, Shaw G, Barry FP, McNamara LM (2012) Osteogenic differentiation of mesenchymal stem cells is regulated by osteocyte and osteoblast cells in a simplified bone niche. Eur Cell Mater 23:13–27PubMed
6.
go back to reference Knothe Tate ML (2003) “Whither flows the fluid in bone?” An osteocyte’s perspective. J Biomech 36:1409–1424CrossRefPubMed Knothe Tate ML (2003) “Whither flows the fluid in bone?” An osteocyte’s perspective. J Biomech 36:1409–1424CrossRefPubMed
7.
go back to reference Kapur S, Baylink DJ, Lau KHW (2002) Fluid flow shear stress stimulates human osteoblast proliferation and differentiation through multiple interacting and competing signal transduction pathways. Bone 32:241–251CrossRef Kapur S, Baylink DJ, Lau KHW (2002) Fluid flow shear stress stimulates human osteoblast proliferation and differentiation through multiple interacting and competing signal transduction pathways. Bone 32:241–251CrossRef
8.
go back to reference McAllister T (2000) Fluid shear stress stimulates prostaglandin and nitric oxide release in bone marrow-derived preosteoclast-like cells. Biochem Bioph Res Co 270:643–648CrossRef McAllister T (2000) Fluid shear stress stimulates prostaglandin and nitric oxide release in bone marrow-derived preosteoclast-like cells. Biochem Bioph Res Co 270:643–648CrossRef
9.
go back to reference Li J, Rose E, Frances D, Sun Y, You L (2012) Effect of oscillating fluid flow stimulation on osteocyte mRNA expression. J Biomech 45:247–251CrossRefPubMed Li J, Rose E, Frances D, Sun Y, You L (2012) Effect of oscillating fluid flow stimulation on osteocyte mRNA expression. J Biomech 45:247–251CrossRefPubMed
10.
go back to reference Nauman EA, Satcher RL, Keaveny TM, Halloran BP, Bikle DD (2001) Osteoblasts respond to pulsatile fluid flow with short-term increases in PGE2 but no change in mineralization. J Appl Physiol 90:1849–1854PubMed Nauman EA, Satcher RL, Keaveny TM, Halloran BP, Bikle DD (2001) Osteoblasts respond to pulsatile fluid flow with short-term increases in PGE2 but no change in mineralization. J Appl Physiol 90:1849–1854PubMed
11.
go back to reference Klein-Nulend J, Semeins CM, Burger EH (1996) Prostaglandin mediated modulation of transforming growth factor-beta metabolism in primary mouse osteoblastic cells in vitro. J Cell Physiol 168:1–7CrossRefPubMed Klein-Nulend J, Semeins CM, Burger EH (1996) Prostaglandin mediated modulation of transforming growth factor-beta metabolism in primary mouse osteoblastic cells in vitro. J Cell Physiol 168:1–7CrossRefPubMed
12.
go back to reference Coughlin TR, Niebur GL (2012) Fluid shear stress in trabecular bone marrow due to low-magnitude high-frequency vibration. J Biomech 45:2222–2229CrossRefPubMed Coughlin TR, Niebur GL (2012) Fluid shear stress in trabecular bone marrow due to low-magnitude high-frequency vibration. J Biomech 45:2222–2229CrossRefPubMed
14.
go back to reference Ziambaras K, Lecanda F, Steinberg TH, Civitelli R (1998) Cyclic stretch enhances gap junctional communication between osteoblastic cells. J Bone Miner Res 13:218–228CrossRefPubMed Ziambaras K, Lecanda F, Steinberg TH, Civitelli R (1998) Cyclic stretch enhances gap junctional communication between osteoblastic cells. J Bone Miner Res 13:218–228CrossRefPubMed
15.
go back to reference Litzenberger JB, Kim JB, Tummala P, Jacobs CR (2010) Beta1 integrins mediate mechanosensitive signaling pathways in osteocytes. Calcif Tissue Int 86:325–332CrossRefPubMedCentralPubMed Litzenberger JB, Kim JB, Tummala P, Jacobs CR (2010) Beta1 integrins mediate mechanosensitive signaling pathways in osteocytes. Calcif Tissue Int 86:325–332CrossRefPubMedCentralPubMed
16.
go back to reference Malone AM, Anderson CT, Tummala P, Kwon RY, Johnston TR, Stearns T, Jacobs CR (2007) Primary cilia mediate mechanosensing in bone cells by a calcium-independent mechanism. Proc Natl Acad Sci U S A 104:13325–13330CrossRefPubMedCentralPubMed Malone AM, Anderson CT, Tummala P, Kwon RY, Johnston TR, Stearns T, Jacobs CR (2007) Primary cilia mediate mechanosensing in bone cells by a calcium-independent mechanism. Proc Natl Acad Sci U S A 104:13325–13330CrossRefPubMedCentralPubMed
17.
go back to reference Hoey DA, Tormey S, Ramcharan S, O’Brien FJ, Jacobs CR (2012) Primary cilia-mediated mechanotransduction in human mesenchymal stem cells. Stem Cells 30:2561–2570CrossRefPubMedCentralPubMed Hoey DA, Tormey S, Ramcharan S, O’Brien FJ, Jacobs CR (2012) Primary cilia-mediated mechanotransduction in human mesenchymal stem cells. Stem Cells 30:2561–2570CrossRefPubMedCentralPubMed
18.
go back to reference Wheatley DN, Wang AM, Strugnell GE (1996) Expression of primary cilia in mammalian cells. Cell Biol Int 20:73–81CrossRefPubMed Wheatley DN, Wang AM, Strugnell GE (1996) Expression of primary cilia in mammalian cells. Cell Biol Int 20:73–81CrossRefPubMed
22.
go back to reference Schwartz EA, Leonard ML, Bizios R, Bowser SS (1997) Analysis and modeling of the primary cilium bending response to fluid shear. Am J Physiol 272:F132–F138PubMed Schwartz EA, Leonard ML, Bizios R, Bowser SS (1997) Analysis and modeling of the primary cilium bending response to fluid shear. Am J Physiol 272:F132–F138PubMed
23.
go back to reference Praetorius HA, Spring KR (2001) Bending the MDCK cell primary cilium increases intracellular calcium. J Membr Biol 184:71–79CrossRefPubMed Praetorius HA, Spring KR (2001) Bending the MDCK cell primary cilium increases intracellular calcium. J Membr Biol 184:71–79CrossRefPubMed
24.
go back to reference Hoey DA, Kelly DJ, Jacobs CR (2011) A role for the primary cilium in paracrine signaling between mechanically stimulated osteocytes and mesenchymal stem cells. Biochem Biophys Res Commun 412:182–187CrossRefPubMedCentralPubMed Hoey DA, Kelly DJ, Jacobs CR (2011) A role for the primary cilium in paracrine signaling between mechanically stimulated osteocytes and mesenchymal stem cells. Biochem Biophys Res Commun 412:182–187CrossRefPubMedCentralPubMed
25.
go back to reference Temiyasathit S, Tang WJ, Leucht P, Anderson CT, Monica SD, Castillo AB, Helms JA, Stearns T, Jacobs CR (2012) Mechanosensing by the primary cilium: deletion of Kif3A reduces bone formation due to loading. PLoS ONE 7:e33368CrossRefPubMedCentralPubMed Temiyasathit S, Tang WJ, Leucht P, Anderson CT, Monica SD, Castillo AB, Helms JA, Stearns T, Jacobs CR (2012) Mechanosensing by the primary cilium: deletion of Kif3A reduces bone formation due to loading. PLoS ONE 7:e33368CrossRefPubMedCentralPubMed
26.
go back to reference Qiu N, Xiao Z, Cao L, Buechel MM, David V, Roan E, Quarles LD (2012) Disruption of Kif3a in osteoblasts results in defective bone formation and osteopenia. J Cell Sci 125:1945–1957CrossRefPubMedCentralPubMed Qiu N, Xiao Z, Cao L, Buechel MM, David V, Roan E, Quarles LD (2012) Disruption of Kif3a in osteoblasts results in defective bone formation and osteopenia. J Cell Sci 125:1945–1957CrossRefPubMedCentralPubMed
27.
go back to reference Bodle JC, Rubenstein CD, Phillips ME, Bernacki SH, Qi J, Banes AJ, Loboa EG (2013) Primary cilia: the chemical antenna regulating human adipose-derived stem cell osteogenesis. PLoS ONE 8:e62554CrossRefPubMedCentralPubMed Bodle JC, Rubenstein CD, Phillips ME, Bernacki SH, Qi J, Banes AJ, Loboa EG (2013) Primary cilia: the chemical antenna regulating human adipose-derived stem cell osteogenesis. PLoS ONE 8:e62554CrossRefPubMedCentralPubMed
28.
go back to reference Whitfield JF (2008) The solitary (primary) cilium—a mechanosensory toggle switch in bone and cartilage cells. Cell Signal 20:1019–1024CrossRefPubMed Whitfield JF (2008) The solitary (primary) cilium—a mechanosensory toggle switch in bone and cartilage cells. Cell Signal 20:1019–1024CrossRefPubMed
29.
go back to reference Gardner K, Arnoczky SP, Lavagnino M (2011) Effect of in vitro stress-deprivation and cyclic loading on the length of tendon cell cilia in situ. J Orthop Res 29:582–587CrossRefPubMed Gardner K, Arnoczky SP, Lavagnino M (2011) Effect of in vitro stress-deprivation and cyclic loading on the length of tendon cell cilia in situ. J Orthop Res 29:582–587CrossRefPubMed
30.
go back to reference McGlashan SR, Knight MM, Chowdhury TT, Joshi P, Jensen CG, Kennedy S, Poole CA (2010) Mechanical loading modulates chondrocyte primary cilia incidence and length. Cell Biol Int 34:441–446CrossRefPubMed McGlashan SR, Knight MM, Chowdhury TT, Joshi P, Jensen CG, Kennedy S, Poole CA (2010) Mechanical loading modulates chondrocyte primary cilia incidence and length. Cell Biol Int 34:441–446CrossRefPubMed
31.
go back to reference Tonna EA, Lampen NM (1972) Electron microscopy of aging skeletal cells. I. Centrioles and solitary cilia. J Gerontol 27:316–324CrossRefPubMed Tonna EA, Lampen NM (1972) Electron microscopy of aging skeletal cells. I. Centrioles and solitary cilia. J Gerontol 27:316–324CrossRefPubMed
32.
go back to reference Uzbekov RE, Maurel DB, Aveline PC, Pallu S, Benhamou CL, Rochefort GY (2012) Centrosome fine ultrastructure of the osteocyte mechanosensitive primary cilium. Microsc Microanal 18:1430–1441CrossRefPubMed Uzbekov RE, Maurel DB, Aveline PC, Pallu S, Benhamou CL, Rochefort GY (2012) Centrosome fine ultrastructure of the osteocyte mechanosensitive primary cilium. Microsc Microanal 18:1430–1441CrossRefPubMed
33.
go back to reference Praetorius HA, Spring KR (2003) The renal cell primary cilium functions as a flow sensor. Curr Opin Nephrol Hypertens 12:517–520CrossRefPubMed Praetorius HA, Spring KR (2003) The renal cell primary cilium functions as a flow sensor. Curr Opin Nephrol Hypertens 12:517–520CrossRefPubMed
34.
go back to reference Tenenbaum HC (1992) Cellular origins and theories of differentiation of bone-forming cells. In: Hall BK (ed) In Bone: The osteoblast and osteocyte. CRC Press, Boca Raton, pp 41–69 Tenenbaum HC (1992) Cellular origins and theories of differentiation of bone-forming cells. In: Hall BK (ed) In Bone: The osteoblast and osteocyte. CRC Press, Boca Raton, pp 41–69
35.
go back to reference Chang MK, Raggatt LJ, Alexander KA, Kuliwaba JS, Fazzalari NL, Schroder K, Maylin ER, Ripoll VM, Hume DA, Pettit AR (2008) Osteal tissue macrophages are intercalated throughout human and mouse bone lining tissues and regulate osteoblast function in vitro and in vivo. J Immunol 181:1232–1244CrossRefPubMed Chang MK, Raggatt LJ, Alexander KA, Kuliwaba JS, Fazzalari NL, Schroder K, Maylin ER, Ripoll VM, Hume DA, Pettit AR (2008) Osteal tissue macrophages are intercalated throughout human and mouse bone lining tissues and regulate osteoblast function in vitro and in vivo. J Immunol 181:1232–1244CrossRefPubMed
36.
go back to reference Weiss L, Geduldig U (1991) Barrier cells: stromal regulation of hematopoiesis and blood cell release in normal and stressed murine bone marrow. Blood 78:975–990PubMed Weiss L, Geduldig U (1991) Barrier cells: stromal regulation of hematopoiesis and blood cell release in normal and stressed murine bone marrow. Blood 78:975–990PubMed
37.
go back to reference Turner CH, Owan I, Alvey T, Hulman J, Hock JM (1998) Recruitment and proliferative responses of osteoblasts after mechanical loading in vivo determined using sustained-release bromodeoxyuridine. Bone 22:463–469CrossRefPubMed Turner CH, Owan I, Alvey T, Hulman J, Hock JM (1998) Recruitment and proliferative responses of osteoblasts after mechanical loading in vivo determined using sustained-release bromodeoxyuridine. Bone 22:463–469CrossRefPubMed
38.
go back to reference Tummala P, Arnsdorf EJ, Jacobs CR (2010) The role of primary cilia in mesenchymal stem cell differentiation: a pivotal switch in guiding lineage commitment. Cell Mol Bioeng 3:207–212CrossRefPubMedCentralPubMed Tummala P, Arnsdorf EJ, Jacobs CR (2010) The role of primary cilia in mesenchymal stem cell differentiation: a pivotal switch in guiding lineage commitment. Cell Mol Bioeng 3:207–212CrossRefPubMedCentralPubMed
39.
go back to reference Fritton JC, Myers ER, Wright TM, van der Meulen MC (2005) Loading induces site-specific increases in mineral content assessed by microcomputed tomography of the mouse tibia. Bone 36:1030–1038CrossRefPubMed Fritton JC, Myers ER, Wright TM, van der Meulen MC (2005) Loading induces site-specific increases in mineral content assessed by microcomputed tomography of the mouse tibia. Bone 36:1030–1038CrossRefPubMed
40.
go back to reference Bayraktar HH, Morgan EF, Niebur GL, Morris GE, Wong EK, Keaveny TM (2004) Comparison of the elastic and yield properties of human femoral trabecular and cortical bone tissue. J Biomech 37:27–35CrossRefPubMed Bayraktar HH, Morgan EF, Niebur GL, Morris GE, Wong EK, Keaveny TM (2004) Comparison of the elastic and yield properties of human femoral trabecular and cortical bone tissue. J Biomech 37:27–35CrossRefPubMed
41.
go back to reference Poole T, Stayner C, McGlashan SR, Parker K, Wiles A, Jennings M, Jensen CG, Johnstone AC, Walker RJ, Eccles MR (2012) Primary cilia defects in the polycystic kidneys from an ovine model of Meckel Gruber syndrome. In: First International Cilia in Development and Disease Scientific Conference. London Poole T, Stayner C, McGlashan SR, Parker K, Wiles A, Jennings M, Jensen CG, Johnstone AC, Walker RJ, Eccles MR (2012) Primary cilia defects in the polycystic kidneys from an ovine model of Meckel Gruber syndrome. In: First International Cilia in Development and Disease Scientific Conference. London
42.
go back to reference Poole CA, Zhang ZJ, Ross JM (2001) The differential distribution of acetylated and detyrosinated alpha-tubulin in the microtubular cytoskeleton and primary cilia of hyaline cartilage chondrocytes. J Anat 199:393–405CrossRefPubMedCentralPubMed Poole CA, Zhang ZJ, Ross JM (2001) The differential distribution of acetylated and detyrosinated alpha-tubulin in the microtubular cytoskeleton and primary cilia of hyaline cartilage chondrocytes. J Anat 199:393–405CrossRefPubMedCentralPubMed
43.
go back to reference Xiao Z, Zhang S, Mahlios J, Zhou G, Magenheimer BS, Guo D, Dallas SL, Maser R, Calvet JP, Bonewald L, Quarles LD (2006) Cilia-like structures and polycystin-1 in osteoblasts/osteocytes and associated abnormalities in skeletogenesis and Runx2 expression. J Biol Chem 281:30884–30895CrossRefPubMedCentralPubMed Xiao Z, Zhang S, Mahlios J, Zhou G, Magenheimer BS, Guo D, Dallas SL, Maser R, Calvet JP, Bonewald L, Quarles LD (2006) Cilia-like structures and polycystin-1 in osteoblasts/osteocytes and associated abnormalities in skeletogenesis and Runx2 expression. J Biol Chem 281:30884–30895CrossRefPubMedCentralPubMed
44.
go back to reference McNamara LM, Majeska RJ, Weinbaum S, Friedrich V, Schaffler MB (2009) Attachment of osteocyte cell processes to the bone matrix. Anat Rec (Hoboken) 292:355–363CrossRef McNamara LM, Majeska RJ, Weinbaum S, Friedrich V, Schaffler MB (2009) Attachment of osteocyte cell processes to the bone matrix. Anat Rec (Hoboken) 292:355–363CrossRef
45.
go back to reference Besschetnova TY, Kolpakova-Hart E, Guan Y, Zhou J, Olsen BR, Shah JV (2010) Identification of signaling pathways regulating primary cilium length and flow-mediated adaptation. Curr Biol 20:182–187CrossRefPubMedCentralPubMed Besschetnova TY, Kolpakova-Hart E, Guan Y, Zhou J, Olsen BR, Shah JV (2010) Identification of signaling pathways regulating primary cilium length and flow-mediated adaptation. Curr Biol 20:182–187CrossRefPubMedCentralPubMed
Metadata
Title
Primary Cilia Exist in a Small Fraction of Cells in Trabecular Bone and Marrow
Authors
Thomas R. Coughlin
Muriel Voisin
Mitchell B. Schaffler
Glen L. Niebur
Laoise M. McNamara
Publication date
01-01-2015
Publisher
Springer US
Published in
Calcified Tissue International / Issue 1/2015
Print ISSN: 0171-967X
Electronic ISSN: 1432-0827
DOI
https://doi.org/10.1007/s00223-014-9928-6

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