Effects of a p38 MAP kinase inhibitor on bone ingrowth and tissue differentiation in rabbit chambers.
The effects of an oral p38 mitogen-activated protein kinase (MAPK) inhibitor and polyethylene particles separately and together on tissue differentiation in the bone harvest chamber (BHC) in rabbits over a 3-week treatment period were investigated. The harvested tissue was analyzed histomorphometrically for markers of bone formation (percentage of bone area), osteoblasts (alkaline phosphatase staining), and osteoclasts (CD51, the alpha chain of the vitronectin receptor). Polyethylene particles decreased the percentage of bone ingrowth and staining for alkaline phosphatase. The p38 MAPK inhibitor alone decreased alkaline phosphatase staining. When the oral p38 MAPK inhibitor was given and the chamber contained polyethylene particles, there was a suppression of bone ingrowth and alkaline phosphatase staining. In contrast to oral non-steroidal anti-inflammatory drugs (NSAIDs) and local Interleukin-1 receptor antagonist (IL-1ra) administration, the oral p38 MAPK inhibitor alone did not suppress bone formation when given during the initial phase of tissue differentiation. Particle-induced inflammation and the foreign body reaction were not curtailed when the p38 MAPK inhibitor was given simultaneously with particles. Additional experiments are needed to establish the efficacy of p38 MAPK inhibitor administration on mitigating an established inflammatory and foreign body reaction that parallels the clinical situation more closely.
Goodman
S B
SB
Department of Orthopaedic Surgery, Stanford University, Stanford, California, USA. goodbone@stanford.edu
Ma
T
T
Spanogle
J
J
Chiu
R
R
Miyanishi
K
K
Oh
K
K
Plouhar
P
P
Wadsworth
S
S
Smith
R L
RL
D000284:Administration, Oral; D000818:Animals; D001672:Biocompatible Materials; D015194:Diffusion Chambers, Culture; D007595:Joint Prosthesis / Q000009:adverse effects; D008297:Male; D008422:Materials Testing; D016348:Osseointegration / Q000187:drug effects*; D010014:Osteolysis / Q000209:etiology / Q000517:prevention & control; D011095:Polyethylenes; D011475:Prosthesis Failure; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D011817:Rabbits; D013977:Tibia / Q000473:pathology / Q000601:surgery; D023822:Tissue Engineering; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*
D001672:Biocompatible Materials; D011095:Polyethylenes; D047428:Protein Kinase Inhibitors; C111601:ultra-high molecular weight polyethylene; D048051:p38 Mitogen-Activated Protein Kinases