Prostaglandins in inflammatory bone pathology: Mechanism and therapeutic benefit of etodolac

M. A. Hayward, G. A. Howard, R. G. Neuman, D. D. Wood, B. M. Weichman, D. C. Van Sickle

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

To investigate the role of PGE2 in the development of bone and joint pathology in rat adjuvant arthritis, hindlimb paws were evaluated by calcified tissue histologic techniques focusing on histochemical visualization of cartilage and bone lesions. Case studies of hindlimbs from normal, adjuvant arthritic, and etodolac-treated arthritic rats demonstrated the association of disease severity with inflammation, chondromalacia, replacement of adipose bone marrow with a fibroid marrow, osteoclastic bone resorption, synovial cysts, and pannus formation within the joints. Extensive periosteal intramembranous bone formation was temporally associated with joint destruction and medullary tissue pathology. In vivo data were correlated with in vitro effects of inflammatory mediators (IL-1, PGE2) on bone resorption. Etodolac blocked bone explant PGE2 accumulation at concentrations of 10-7M and higher, and inhibited bone resorption at concentrations of 10-5M and higher. The data indicate that in vitro and in vivo models of bone metabolism are well correlated regarding prostaglandin synthesis; that the inflammatory mediator PGE2 is largely responsible for the involvement of skeletal tissue in the adjuvant arthritis model; and that the effects of etodolac are specifically mediated by its ability to inhibit PGE2 accumulation in vivo.

Original languageEnglish (US)
Pages (from-to)310-318
Number of pages9
JournalAgents and Actions
Volume26
Issue number3-4
DOIs
StatePublished - Mar 1 1989
Externally publishedYes

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology (medical)

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    Hayward, M. A., Howard, G. A., Neuman, R. G., Wood, D. D., Weichman, B. M., & Van Sickle, D. C. (1989). Prostaglandins in inflammatory bone pathology: Mechanism and therapeutic benefit of etodolac. Agents and Actions, 26(3-4), 310-318. https://doi.org/10.1007/BF01967295