TREATMENT WITH THE NON-IONIC SURFACTANT POLOXAMER P188

REDUCES DNA FRAGMENTATION IN CELLS FROM BOVINE CHONDRAL EXPLANTS

EXPOSED TO INJURIOUS UNCONFINED COMPRESSION

 

July 22, 2005

 

Biomechanics and Modeling in Mechanobiology Journal

 

Baars DC; Rundell SA; Haut RC

 

ABSTRACT:

            Excessive mechanical loading to a joint has been linked with the development of posttraumatic 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 hours 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 hour 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 hour, 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 fragmentation of their DNA.

 

 

Orthopaedic Biomechanics Laboratories,

 College of Osteopathic Medicine,

 Michigan State University,

 East Lansing, Michigan 48824

 

Please address correspondence to:

 

Roger C. Haut, Ph.D.,

 Orthopaedic Biomechanics Laboratory,

 College of Osteopathic Medicine,

 A414 East Fee Hall,

 Michigan State University,

 East Lansing, MI 48824,

Tel:  (517)355-0320,

 Fax:  (517)353-0789,

  E-mail:  haut@msu.edu