Haas, N. P. Callus modulation—Fiction or reality?. Chirurg 71, 987–988. https://doi.org/10.1007/s001040051171 (2000).
Google Scholar
Delaine-Smith, R. M. & Reilly, G. C. Mesenchymal stem cell responses to mechanical st`imuli. Muscles Ligaments Tendons J. 2, 169–180 (2012).
Google Scholar
Fahy, N., Alini, M. & Stoddart, M. J. Mechanical stimulation of mesenchymal stem cells: Implications for cartilage tissue engineering. J. Orthop. Res. 36, 52–63. https://doi.org/10.1002/jor.23670 (2018).
Google Scholar
Luo, Z. J. & Seedhom, B. B. Light and low-frequency pulsatile hydrostatic pressure enhances extracellular matrix formation by bone marrow mesenchymal cells: An in-vitro study with special reference to cartilage repair. Proc. Inst. Mech. Eng. H 221, 499–507. https://doi.org/10.1243/09544119JEIM199 (2007).
Google Scholar
Steadman, J. R., Rodkey, W. G. & Rodrigo, J. J. Microfracture: Surgical technique and rehabilitation to treat chondral defects. Clin. Orthop. Relat. Res. https://doi.org/10.1097/00003086-200110001-00033 (2001).
Google Scholar
Buckwalter, J. A. & Mankin, H. J. Articular cartilage repair and transplantation. Arthritis Rheum. 41, 1331–1342. https://doi.org/10.1002/1529-0131(199808)41:8%3c1331::AID-ART2%3e3.0.CO;2-J (1998).
Google Scholar
Hunziker, E. B. Articular cartilage repair: Basic science and clinical progress. A review of the current status and prospects. Osteoarthritis Cartil. 10, 432–463. https://doi.org/10.1053/joca.2002.0801 (2002).
Google Scholar
Erggelet, C. & Vavken, P. Microfracture for the treatment of cartilage defects in the knee joint—A golden standard?. J. Clin. Orthop. Trauma 7, 145–152. https://doi.org/10.1016/j.jcot.2016.06.015 (2016).
Google Scholar
Johnstone, B., Hering, T. M., Caplan, A. I., Goldberg, V. M. & Yoo, J. U. In vitro chondrogenesis of bone marrow-derived mesenchymal progenitor cells. Exp. Cell Res. 238, 265–272. https://doi.org/10.1006/excr.1997.3858 (1998).
Google Scholar
Barry, F., Boynton, R. E., Liu, B. & Murphy, J. M. Chondrogenic differentiation of mesenchymal stem cells from bone marrow: Differentiation-dependent gene expression of matrix components. Exp. Cell Res. 268, 189–200. https://doi.org/10.1006/excr.2001.5278 (2001).
Google Scholar
Li, Z., Kupcsik, L., Yao, S. J., Alini, M. & Stoddart, M. J. Mechanical load modulates chondrogenesis of human mesenchymal stem cells through the TGF-beta pathway. J. Cell Mol. Med. 14, 1338–1346. https://doi.org/10.1111/j.1582-4934.2009.00780.x (2010).
Google Scholar
Behrendt, P. et al. Articular joint-simulating mechanical load activates endogenous TGF-beta in a highly cellularized bioadhesive hydrogel for cartilage repair. Am. J. Sports Med. 48, 210–221. https://doi.org/10.1177/0363546519887909 (2020).
Google Scholar
Sumanasinghe, R. D., Bernacki, S. H. & Loboa, E. G. Osteogenic differentiation of human mesenchymal stem cells in collagen matrices: Effect of uniaxial cyclic tensile strain on bone morphogenetic protein (BMP-2) mRNA expression. Tissue Eng. 12, 3459–3465. https://doi.org/10.1089/ten.2006.12.3459 (2006).
Google Scholar
Jaiswal, N., Haynesworth, S. E., Caplan, A. I. & Bruder, S. P. Osteogenic differentiation of purified, culture-expanded human mesenchymal stem cells in vitro. J. Cell Biochem. 64, 295–312 (1997).
Google Scholar
Halvorsen, Y. D. et al. Extracellular matrix mineralization and osteoblast gene expression by human adipose tissue-derived stromal cells. Tissue Eng. 7, 729–741. https://doi.org/10.1089/107632701753337681 (2001).
Google Scholar
Hofseth, L. J. et al. Nitric oxide-induced cellular stress and p53 activation in chronic inflammation. Proc. Natl. Acad. Sci. USA 100, 143–148. https://doi.org/10.1073/pnas.0237083100 (2003).
Google Scholar
Forstermann, U., Xia, N. & Li, H. Roles of vascular oxidative stress and nitric oxide in the pathogenesis of atherosclerosis. Circ. Res. 120, 713–735. https://doi.org/10.1161/CIRCRESAHA.116.309326 (2017).
Google Scholar
Fox, S. W., Chambers, T. J. & Chow, J. W. Nitric oxide is an early mediator of the increase in bone formation by mechanical stimulation. Am. J. Physiol. 270, E955-960. https://doi.org/10.1152/ajpendo.1996.270.6.E955 (1996).
Google Scholar
Montgomery, D. C. Design and Analysis of Experiments 8th edn. (Wiley, 2013).
Oehlert, G. W. A First Course in Design and Analysis of Experiments. 2010. http://users.stat.umn.edu/~gary/book/fcdae.pdf. Accessed 10 August 2020.
Gardner, O. F., Alini, M. & Stoddart, M. J. Mesenchymal stem cells derived from human bone marrow. Methods Mol. Biol. (Clifton, N.J.) 1340, 41–52. https://doi.org/10.1007/978-1-4939-2938-2_3 (2015).
Google Scholar
Li, Z., Kupcsik, L., Yao, S. J., Alini, M. & Stoddart, M. J. Chondrogenesis of human bone marrow mesenchymal stem cells in fibrin-polyurethane composites. Tissue Eng. Part A 15, 1729–1737. https://doi.org/10.1089/ten.tea.2008.0247 (2009).
Google Scholar
Gardner, O. F. W. et al. Asymmetrical seeding of MSCs into fibrin-poly(ester-urethane) scaffolds and its effect on mechanically induced chondrogenesis. J. Tissue Eng. Regen. Med. 11, 2912–2921. https://doi.org/10.1002/term.2194 (2017).
Google Scholar
Wimmer, M. A. et al. Tribology approach to the engineering and study of articular cartilage. Tissue Eng. 10, 1436–1445. https://doi.org/10.1089/ten.2004.10.1436 (2004).
Google Scholar
Gardner, O. F. W., Fahy, N., Alini, M. & Stoddart, M. J. Joint mimicking mechanical load activates TGFbeta1 in fibrin-poly(ester-urethane) scaffolds seeded with mesenchymal stem cells. J. Tissue Eng. Regen. Med. 11, 2663–2666. https://doi.org/10.1002/term.2210 (2017).
Google Scholar
Schatti, O. et al. A combination of shear and dynamic compression leads to mechanically induced chondrogenesis of human mesenchymal stem cells. Eur. Cell Mater. 22, 214–225 (2011).
Google Scholar
Farndale, R. W., Buttle, D. J. & Barrett, A. J. Improved quantitation and discrimination of sulphated glycosaminoglycans by use of dimethylmethylene blue. Biochim. Biophys. Acta 883, 173–177. https://doi.org/10.1016/0304-4165(86)90306-5 (1986).
Google Scholar
R: A Language and Environment for Statistical Computing (2020).
RStudio: Integrated Development for R. RStudio (RStudio, PBC, 2020).
Li, Z., Yao, S. J., Alini, M. & Stoddart, M. J. Chondrogenesis of human bone marrow mesenchymal stem cells in fibrin-polyurethane composites is modulated by frequency and amplitude of dynamic compression and shear stress. Tissue Eng. Part A 16, 575–584. https://doi.org/10.1089/ten.TEA.2009.0262 (2010).
Google Scholar
Field, A. P., Miles, J. & Field, Z. Discovering Statistics Using R (Sage, 2012).
Rosenthal, R. Meta-Analytic Procedures for Social Research Rev. (Sage Publications, 1991).
Google Scholar
Steward, A. J. & Kelly, D. J. Mechanical regulation of mesenchymal stem cell differentiation. J. Anat. 227, 717–731. https://doi.org/10.1111/joa.12243 (2015).
Google Scholar
Ahamed, J. et al. In vitro and in vivo evidence for shear-induced activation of latent transforming growth factor-beta1. Blood 112, 3650–3660. https://doi.org/10.1182/blood-2008-04-151753 (2008).
Google Scholar
Albro, M. B. et al. Shearing of synovial fluid activates latent TGF-beta. Osteoarthritis Cartil. 20, 1374–1382. https://doi.org/10.1016/j.joca.2012.07.006 (2012).
Google Scholar
Ohno, M., Cooke, J. P., Dzau, V. J. & Gibbons, G. H. Fluid shear stress induces endothelial transforming growth factor beta-1 transcription and production. Modulation by potassium channel blockade. J. Clin. Invest. 95, 1363–1369. https://doi.org/10.1172/JCI117787 (1995).
Google Scholar
Wipff, P. J., Rifkin, D. B., Meister, J. J. & Hinz, B. Myofibroblast contraction activates latent TGF-beta1 from the extracellular matrix. J. Cell Biol. 179, 1311–1323. https://doi.org/10.1083/jcb.200704042 (2007).
Google Scholar
Tanaka, S. M. et al. Osteoblast responses one hour after load-induced fluid flow in a three-dimensional porous matrix. Calcif. Tissue Int. 76, 261–271. https://doi.org/10.1007/s00223-004-0238-2 (2005).
Google Scholar
Zahedmanesh, H. et al. Deciphering mechanical regulation of chondrogenesis in fibrin-polyurethane composite scaffolds enriched with human mesenchymal stem cells: A dual computational and experimental approach. Tissue Eng. Part A 20, 1197–1212. https://doi.org/10.1089/ten.TEA.2013.0145 (2014).
Google Scholar
Sato, M. et al. Mechanical tension-stress induces expression of bone morphogenetic protein (BMP)-2 and BMP-4, but not BMP-6, BMP-7, and GDF-5 mRNA, during distraction osteogenesis. J. Bone Miner. Res. 14, 1084–1095. https://doi.org/10.1359/jbmr.1999.14.7.1084 (1999).
Google Scholar
Kopf, J., Petersen, A., Duda, G. N. & Knaus, P. BMP2 and mechanical loading cooperatively regulate immediate early signalling events in the BMP pathway. BMC Biol. https://doi.org/10.1186/1741-7007-10-37 (2012).
Google Scholar
D’Angelo, M. et al. MMP-13 is induced during chondrocyte hypertrophy. J. Cell Biochem. 77, 678–693 (2000).
Google Scholar
Tsuji, K. et al. BMP2 activity, although dispensable for bone formation, is required for the initiation of fracture healing. Nat. Genet. 38, 1424–1429. https://doi.org/10.1038/ng1916 (2006).
Google Scholar
Ghosh-Choudhury, N. et al. Autoregulation of mouse BMP-2 gene transcription is directed by the proximal promoter element. Biochem. Biophys. Res. Commun. 286, 101–108. https://doi.org/10.1006/bbrc.2001.5351 (2001).
Google Scholar
Nasrabadi, D., Rezaeiani, S., Eslaminejad, M. B. & Shabani, A. Improved protocol for chondrogenic differentiation of bone marrow derived mesenchymal stem cells-effect of PTHrP and FGF-2 on TGFbeta1/BMP2-induced chondrocytes hypertrophy. Stem Cell Rev. Rep. 14, 755–766. https://doi.org/10.1007/s12015-018-9816-y (2018).
Google Scholar
Li, Z., Kupcsik, L., Alini, M., Yao, S. J. & Stoddart, M. Mechanical load modulates chondrogenesis of human mesenchymal stem cells through the TGF-beta pathway. J. Cell Mol. Med. 14, 1338–1346 (2010).
Google Scholar
Kupcsik, L., Stoddart, M. J., Li, Z., Benneker, L. M. & Alini, M. Improving chondrogenesis: Potential and limitations of SOX9 gene transfer and mechanical stimulation for cartilage tissue engineering. Tissue Eng. Part A 16, 1845–1855. https://doi.org/10.1089/ten.TEA.2009.0531 (2010).
Google Scholar
Gardner, O. F., Fahy, N., Alini, M. & Stoddart, M. J. Differences in human mesenchymal stem cell secretomes during chondrogenic induction. Eur. Cell Mater. 31, 221–235 (2016).
Google Scholar
Stoddart, M. J., Richards, R. G. & Alini, M. In vitro experiments with primary mammalian cells: To pool or not to pool?. Eur. Cell Mater. 24, i–ii (2012).
Google Scholar
Schad, D. J., Vasishth, S., Hohenstein, S. & Kliegl, R. How to capitalize on a priori contrasts in linear (mixed) models: A tutorial. J. Memory Lang. https://doi.org/10.1016/j.jml.2019.104038 (2020).
Google Scholar
