Abstract
Excessive mechanical loading to a joint has been linked with the development of post-traumatic osteoarthritis (OA). Among the suspected links between impact trauma to a joint and associated degeneration of articular cartilage is an acute reduction in chondrocyte viability. Recently, the non-ionic surfactant poloxamer 188 (P188) has been shown to reduce by approximately 50% the percentage of non-viable chondrocytes 24 h post-injury in chondral explants exposed to 25 MPa of unconfined compression. There is a question whether these acutely ‘saved’ chondrocytes will continue to degrade over time, as P188 is only thought to act by acute repair of damaged cell membranes. In order to investigate the degradation of traumatized chondrocytes in the longer term, the current study utilized TUNEL staining to document the percentage of cells suffering DNA fragmentation with and without an immediate 24 h period of exposure of the explants to P188 surfactant. In the current study, as in the previous study by this laboratory, chondral explants were excised from bovine metacarpophalangeal joints and subjected to 25 MPa of unconfined compression. TUNEL staining was performed at 1 h, 4 days, and 7 days post-impact. The current study found that P188 was effective in reducing the percentage of cells with DNA fragmentation in impacted explants by approximately 45% at 4 and 7 days post-impact. These data suggest that early P188 intervention was effective in preventing DNA fragmentation of injured chondrocytes. The current hypothesis is that this process was mitigated by the acute repair of damaged plasma membranes by the non-ionic surfactant P188, and that most repaired cells did not continue to degrade as measured by the fragmentation of their DNA.
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References
Atkinson PJ, Haut RC (1995) Subfracture insult to the human cadaver patellofemoral joint produces occult injury. J Orthop Res 13:936–944
Atkinson PJ, Haut RC (2001) Impact responses of the flexed human knee using a deformable impact interface. J Biomech Eng 123(3):205–211
Barbee KA, Ford CM, Blackman BR, Thibault LE (1992) Neural cell injury: characterization and treatment strategy. In: Yang K (ed) 2nd injury prevention through biomechanics symposium proceedings, CDC
Chen CT, Burton-Wurster N, Borden C, Hueffer K, Bloom SE, Lust G (2001) Chondrocyte necrosis and apoptosis in impact damaged articular cartilage. J Orthop Res 19:703–711
Clements KM, Burton-Wurster N, Lust G (2004) The spread of cell death from impact damaged cartilage: lack of evidence for the role of nitric oxide and caspases. Osteoarth Cartil 12:577–585 DOI 10.1016/j.joca.2004.04.006
Costouros JG, Dang AC, Huberti H (2004) Comparison of chondrocyte apoptosis in vivo and in vitro following acute osteochondral injury. J Orthop Res 22:678–683
Davis M, Ettinger W, Neuhaus J, Cho S, Hauck W (1989) The association of knee injury and obesity with unilateral and bilateral osteoarthritis of the knee. Am J Epidemiol 130(2):278–288
D’Lima DD, Hashimoto S, Chen PC, Colwell Jr CW, Lotz MK (2001) Human chondrocyte apoptosis in response to mechanical injury. Osteoarthr Cartil 9:712–719 DOI 10.1053/joca.2001.0468
Duke RC, Ojcius DM, Young JDE (1996) Cell suicide in health and disease. Sci Am 275:80–87
Ewers B, Krueger J, Dvoracek-Driksna D, Orth M, Haut RC (2001a) Chondrocyte viability decreases over 24 hours post-impact in a mechanically traumatized cartilage explant. In: 47th annual meeting Orthopaedic Research Society, vol 47, p 431
Ewers BJ, Dvoracek-Driksna D, Orth MW, Haut RC (2001b) The extent of matrix damage and chondrocyte death in mechanically traumatized articular cartilage explants depends on rate of loading. J Orthop Res 19:779–784
Felson DT (2004) An update on the pathogenesis and epidemiology of osteoarthritis. Radiol Clin North Am 42(1):1–9
Grasl-Kraupp B, Ruttkay-Nedecky B, Koudelka H, Bukowska K, Bursch W, Schulte-Hermann R (1995) In situ detection of fragmented DNA (TUNEL assay) fails to discriminate among apoptosis, necrosis, and autolytic cell death: a cautionary note. Hepatology 21:1465–1468
Grogan SP, Aklin B, Frenz M, Brunner T, Schaffner T (2002) In vitro model for the study of necrosis and apoptosis in native cartilage. J Pathol 198:5–13 DOI 10.1002/path.1169
Hashimoto S, Takahashi K, Amiel D, Coutts RD, Lotz M (1998) Chondrocyte apoptosis and nitric oxide production during experimentally induced osteoarthritis. Arthritis Rheum 41:1266–1274
Kerin A, Patwari P, Kuettner K, Cole A, Grodzinsky A (2002) Molecular basis of osteoarthritis: biomechanical aspects. Cell Mol Life Sci 59:27–35
Krueger JA, Thisse P, Ewers BJ, Dvoracek-Driksna D, Orth MW, Haut RC (2003) The extent and distribution of cell death and matrix damage in impacted chondral explants varies with the presence of underlying bone. J Biomech Eng 125(1):114–119
Lee RC, River LP, Pan F, Ji L, Wollmann RL (1992) Surfactant-induced sealing of electropermeabilized skeletal muscle membranes in vivo. Proc Nat Acad Sci 89:4524–4528
Levin A, Burton-Wurster N, Chen CT, Lust G (2001) Intercellular signaling as a cause of cell death in cyclically impacted cartilage explants. Osteoarth Cartil 9:702–711 DOI 10.1053/joca.2001.0467
Lewis JL, Deloria LB, Oyen-Tiesma M, Thompson RC, Ericson M, Oegema TR (2003) Cell death after cartilage impact occurs around matrix cracks. J Orthop Res 21:881–887
Marks JD, Pan CY, Bushell T, Cromie W, Lee RC (2001) Amphiphilic, tri-block copolymers provide potent membrane-targeted neuroprotection. FASEB J 15:1107–1109 DOI 10.1096/fj.00-054fje
Morel V, Quinn TM (2004) Cartilage injury by ramp compression near the gel diffusion rate. J Orthop Res 22:145–151
Padanilam JT, Bischof JC, Lee RC, Cravalho EG, Tompkins RG, Yarmush ML, Toner M (1994) Effectiveness of poloxamer 188 in arresting calcein leakage from thermally damaged isolated skeletal muscle cells. Ann NY Acad Sci 720:111–123
Phillips DM, Haut RC (2004) The use of a non-ionic surfactant (P188) to save chondrocytes from necrosis following impact loading of chondral explants. J Orthop Res 22[5]:1135–1142
Quinn TM, Allen RG, Schalet BJ, Perumbuli P, Hunziker EB (2001) Matrix and cell injury due to sub-impact loading of adult bovine articular cartilage explants: Effects of strain rate and peak stress. J Orthop Res 19:242–249
Serbest G (2003) In vitro neuronal cell injury model: characterization and treatment strategies. PhD Dissertation, Drexel University 66:125–131
Togo T, Alderton JM, Bi G, Steinhardt RA (1999) The mechanism of facilitated membrane resealing. J Cell Sci 112:719–731
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Baars, D.C., Rundell, S.A. & Haut, R.C. Treatment with the Non-ionic Surfactant Poloxamer P188 Reduces DNA Fragmentation in Cells from Bovine Chondral Explants Exposed to Injurious Unconfined Compression. Biomech Model Mechanobiol 5, 133–139 (2006). https://doi.org/10.1007/s10237-006-0024-3
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DOI: https://doi.org/10.1007/s10237-006-0024-3
Keywords
- Poloxamer
- Damage Cell Membrane
- Unconfined Compression
- Cartilage Explants
- P188 Treatment