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Large magnitude of force leads to NO-mediated cell shrinkage in single osteocytes implying an initial apoptotic response

Nakao, Nobuhiko Mori, Izumi Sunaga, Junko Adachi, Taiji 京都大学 DOI:10.1016/j.jbiomech.2021.110245

2021.03.05

概要

Damage accumulation in the bone under continuous daily loading causes local mechanical overloading known to induce osteocyte apoptosis, which promotes bone resorption to repair bone damage. However, only a few studies have investigated the mechanism of apoptosis in mechanically overloaded osteocytes. As mechanically stimulated osteocytes produce nitric oxide (NO), which triggers apoptosis in various cell types, we aimed to elucidate the mechanism underlying apoptosis in mechanically overloaded osteocytes, focusing on intracellular NO. To investigate the effects of force magnitude on apoptosis and intracellular NO production, we isolated osteocytes from DMP1-EGFP mice and subjected them to quantitative local forces via fibronectin-coated micro beads targeting integrin on the cell surface using a magnetic tweezer. Cell shrinkage was microscopically examined, and intracellular NO production was visualized using DAR-4 M. Mechanical stimulation revealed relationships between force magnitude, apoptosis, and intracellular NO production. The application of a smaller force resulted in no significant cell shrinkage or intracellular NO production; however, a larger force caused a rapid increase in intracellular NO production followed by cell shrinkage. Besides, intracellular NOS (NO synthase) inhibition and NO donation revealed the pro-apoptotic roles of NO in osteocytes. L-NAME (NOS inhibitor)-treated cells displayed no significant shrinkage under a larger force, whereas SNP (NO donor)-treated cells showed cell shrinkage and Annexin V fluorescence, indicating apoptosis. Collectively, our study demonstrates that larger force leads to NO production-mediated osteocyte shrinkage, implying an initial apoptotic response and highlighting the importance of NO production in bone damage.

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参考文献

Adachi, T., Aonuma, Y., Ito, S., Tanaka, M., Hojo, M., Takano-Yamamoto, T., Kamioka,

H., 2009a. Osteocyte calcium signaling response to bone matrix deformation. J.

Biomech. 42, 2507–2512. https://doi.org/10.1016/j.jbiomech.2009.07.006.

Adachi, T., Aonuma, Y., Tanaka, M., Hojo, M., Takano-Yamamoto, T., Kamioka, H.,

2009b. Calcium response in single osteocytes to locally applied mechanical

stimulus: Differences in cell process and cell body. J. Biomech. 42, 1989–1995.

https://doi.org/10.1016/j.jbiomech.2009.04.034.

Adair, B.D., Xiong, J., Maddock, C., Goodman, S.L., Arnaout, M.A., Yeager, M., 2005.

Three-dimensional EM structure of the ectodomain of integrin aVb3 in a

complex with fibronectin. J. Cell Biol. 168, 1109–1118. https://doi.org/10.1083/

jcb.200410068.

Albina, J.E., Cui, S.J., Mateo, R.B., Reichner, J.S., 1993. Nitric oxide-mediated apoptosis

in murine peritoneal macrophages. J. Immunol. 150, 5080–5085. https://doi.

org/10.1016/0169-4758(93)90226-6.

Andrade, R., Crisol, L., Prado, R., Boyano, M.D., Arluzea, J., Arechaga, J., 2010. Plasma

membrane and nuclear envelope integrity during the blebbing stage of

apoptosis: a time-lapse study. Biol. Cell 102, 25–35. https://doi.org/10.1042/

BC20090077.

Bacabac, R.G., Mizuno, D., Schmidt, C.F., Mackintosh, F.C., Van Loon, J.J.W.A., KleinNulend, J., Smit, T.H., 2008. Round versus flat : Bone cell morphology, elasticity,

and mechanosensing. J. Biomech. 41, 1590–1598. https://doi.org/10.1016/j.

jbiomech.2008.01.031.

Bakker, A.D., da Silva, V.C., Krishnan, R., Bacabac, R.G., Blaauboer, M.E., Lin, Y.C.,

Marcantonio, R.A.C., Cirelli, J.A., J, K.-N., 2009. Tumor Necrosis Factor a and

Interleukin-1b Modulate Calcium and Nitric Oxide Signaling in Mechanically

Stimulated Osteocytes. Arthritis Rheum. 60, 3336–3345. 10.1002/art.24920

Balligand, J.L., Ungureanu-Longrois, D., Simmons, W.W., Pimental, D., Malinski, T.A.,

Kapturczak, M., Taha, Z., Lowenstein, C.J., Davidoff, A.J., Kelly, R.A., Smith, T.W.,

Michel, T., 1994. Cytokine-inducible nitric oxide synthase (iNOS) expression in

cardiac myocytes. Characterization and regulation of iNOS expression and

detection of iNOS activity in single cardiac myocytes in vitro. J. Biol. Chem. 269,

27580–27588.

Blanco, F.J., Ochs, R.L., Schwarz, H., Lotz, M., 1995. Chondrocyte apoptosis induced

by nitric oxide. Am. J. Pathol. 146, 75–85.

Bredt, D.S., Snyder, S.H., 1990. Isolation of nitric oxide synthetase, a calmodulinrequiring enzyme. Proc. Natl. Acad. Sci. U. S. A. 87, 682–685. https://doi.org/

10.1073/pnas.87.2.682.

Cabahug-zuckerman, P., Jr, R.F.S., Majeska, R.J., Thi, M.M., Spray, D.C., Weinbaum, S.,

Schaffler, M.B., 2018. Potential Role for a Specialized b3 Integrin-Based

Structure On Osteocyte Processes in Bone Mechanosensation. J. Orthop. Res.

36, 642–652. 10.1002/jor.23792

Cardoso, L., Herman, B.C., Verborgt, O., Laudier, D., Majeska, R.J., Schaffler, M.B.,

2009. Osteocyte Apoptosis Controls Activation of Intracortical Resorption in

Response to Bone Fatigue. J. Bone Miner. Res. 24, 597–605. https://doi.org/

10.1359/jbmr.081210.

Chen, R.M., Chen, T.L., Chiu, W.T., Chang, C.C., 2005. Molecular mechanism of nitric

oxide-induced osteoblast apoptosis. J. Orthop. Res. 23, 462–468. https://doi.org/

10.1016/j.orthres.2004.08.011.

Chiou, W.-F., Chen, C.-F., Lin, J.-J., 2000. Mechanisms of suppression of inducible

nitric oxide synthase (iNOS) expression in RAW 264.7 cells by andrographolide.

Br. J. Pharmacol. 129, 1553–1560. https://doi.org/10.1038/sj.bjp.0703191.

Demchenko, A.P., 2013. Beyond annexin V: fluorescence response of cellular

membranes to apoptosis. Cytotechnology 65, 157–172. https://doi.org/10.1007/

s10616-012-9481-y.

Dimmeler, S., Hermann, C., Galle, J., Zeiher, A.M., 1999. Upregulation of Superoxide

Dismutase and Nitric Oxide Synthase Mediates the Apoptosis-Suppressive

Effects of Shear Stress on Endothelial Cells. Arterioscler. Thromb. Vasc. Biol. 19,

656–664. https://doi.org/10.1161/01.ATV.19.3.656.

Forstermann, U., Pollock, J.S., Schmidt, H.H.H.W., Heller, M., Murad, F., 1991.

Calmodulin-dependent endothelium-derived relaxing factor/nitric oxide

synthase activity is present in the particulate and cytosolic fractions of

bovine aortic endothelial cells. Proc. Natl. Acad. Sci. U. S. A. 88, 1788–1792.

https://doi.org/10.1073/pnas.88.5.1788.

Hasegawa, T., Yamamoto, T., Hongo, H., Qiu, Z., Abe, M., Kanesaki, T., Tanaka, K.,

Endo, T., de Freitas, P.H.L., Li, M.Q., Amizuka, N., 2018. Three-dimensional

ultrastructure of osteocytes assessed by focused ion beam-scanning electron

microscopy (FIB-SEM). Histochem. Cell Biol. 149, 423–432. https://doi.org/

10.1007/s00418-018-1645-1.

Hoshi, K., Kawaki, H., Takahashi, I., Takeshita, N., Seiryu, M., Murshid, S.A.,

Masuda, T., Anada, T., Kato, R., Kitaura, H., Suzuki, O., Takano-Yamamoto, T.,

2014. Compressive force-produced CCN2 induces osteocyte apoptosis through

ERK1/2 pathway. J. Bone Miner. Res. 29, 1244–1257. https://doi.org/10.1002/

jbmr.2115.

Kanaoka, K., Kobayashi, Y., Hashimoto, F., Nakashima, T., Shibata, M., Kobayashi, K.,

Kato, Y., Sakai, H., 2000. A Common Downstream Signaling Activity of

Osteoclast Survival Factors That Prevent Nitric Oxide-Promoted osteoclast

apoptosis.

Endocrinology

141,

2995–3005.

https://doi.org/10.1210/

endo.141.8.7603.

Kim, S.-J., Ju, J.-W., Oh, C.-D., Yoon, Y.-M., Song, W.K., Kim, J.-H., Yoo, Y.J., Bang, O.-S.,

Kang, S.-S., Chun, J.-S., 2002. ERK-1/2 and p38 Kinase Oppositely Regulate Nitric

Oxide-induced Apoptosis of Chondrocytes in Association with p53, Caspase-3,

and Differentiation Status. J. Biol. Chem. 277, 1332–1339. https://doi.org/

10.1074/jbc.M107231200.

A Self-archived copy in

Kyoto University Research Information Repository

https://repository.kulib.kyoto-u.ac.jp

N. Nakao, I. Mori, J. Sunaga et al.

Journal of Biomechanics 117 (2021) 110245

D.D., Wink, D.A., 2004. The chemical biology of nitric oxide: Implications in

cellular signaling. Free Radic. Bioligy Med. 45, 18–31. https://doi.org/10.1016/j.

freeradbiomed.2008.03.020.

Tian, Q., Wu, S., Dai, Z., Yang, J., Zheng, J., Zheng, Q., Liu, Y., 2016. Iron overload

induced death of osteoblasts in vitro: involvement of the mitochondrial

apoptotic pathway. PeerJ 4,. https://doi.org/10.7717/peerj.2611 e2611.

Toyosawa, S., Shintani, S., Fujiwara, T., Ooshima, T., Sato, A., Ijuhin, N., Komori, T.,

2001. Dentin Matrix Protein 1 Is Predominantly Expressed in Chicken and Rat

Osteocytes But Not in Osteoblasts. J. Bone Miner. Res. 16, 2017–2026. https://

doi.org/10.1359/jbmr.2001.16.11.2017.

Vashishth, D., Koontz, J., Qiu, S.J., Lundin-Cannon, D., Yeni, Y.N., Schaffler, M.B.,

Fyhrie, D.P., 2000. In Vivo Diffuse Damage in Human Vertebral Trabecular Bone.

Bone 26, 147–152. https://doi.org/10.1016/S8756-3282(99)00253-7.

Vatsa, A., Mizuno, D., Smit, T.H., Schmidt, C.F., Mackintosh, F.C., Klein-Nulend, J.,

2006. Bio imaging of intracellular NO production in single bone cells after

mechanical stimulation. J. Bone Miner. Res. 21, 1722–1728. https://doi.org/

10.1359/JBMR.060720.

Verborgt, O., Gibson, G.J., Schaffler, M.B., 2000. Loss of Osteocyte Integrity in

Association with Microdamage and Bone Remodeling After Fatigue In Vivo. J.

Bone Miner. Res. 15, 60–67. https://doi.org/10.1359/jbmr.2000.15.1.60.

Wang, Y., McNamara, L.M., Schaffler, M.B., Weinbaum, S., 2007. A model for the role

of integrins in flow induced mechanotransduction in osteyocytes. Proc. Natl.

Acad. Sci. U. S. A. 104, 15941–15946. https://doi.org/10.1073/pnas.0707246104.

Yeni, Y.N., Fyhrie, D.P., 2002. Fatigue Damage-Fracture Mechanics Interaction in

Cortical Bone. Bone 30, 509–514. https://doi.org/10.1016/S8756-3282(01)

00696-2.

Yoshioka, Y., Yamamuro, A., Maeda, S., 2003. Nitric oxide at a low concentration

protects murine macrophage RAW264 cells against nitric oxide-induced death

via cGMP signaling pathway. Br. J. Pharmacol. 139, 28–34. https://doi.org/

10.1038/sj.bjp.0705206.

You, L., Weinbaum, S., Cowin, S.C., Schaffler, M.B., 2004. Ultrastructure of the

Osteocyte Process and its Pericellular Matrix. Anat. Rec. Part A - Discov. Mol.

Cell. Evol. Biol. 278A, 505–513. https://doi.org/10.1002/ar.a.20050.

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