POSSIBLE PROTECTIVE ROLE OF PITUITARY ADENYLATE CYCLASE – ACTIVATING POLYPETIDE IN RAT OSTEOARTHRITIS - PRELIMINARY STUDY
Pituitary adenylate-cyclase activating polypeptide (PACAP) is classified as a member of the vasoactive intestinal peptide (VIP)/secretin/glucagon superfamily with two biological active isoforms. PACAP 1-38 being a pleiotropic neuropeptide possess various biological functions. Increasing evidence is already available on its antiapoptotic, antiinflammatory and cytoprotective functions in distinct tissues. Altough PACAP is also proved to play a crucial role in chondro- and osteogenesis, little is known about the possible effect of PACAP in osteoarthritis. We attempted to clarify the potential cytoprotective role of intraarticularly administered PACAP using monosodium-iodoacetate (MIA) induced osteoarthritis rat model. We investigated the possible morphological changes with cartilage-specific histological analysis, the motor performance with RotaRod and horizontal wire grid functional tests. Thermometric measurements of the inflammated knee joints were also performed and evaluated. Additional administration of PACAP induced significantly higher cell-survival and moderate alterations in GAG/ Collagen Type II production of articular chondrocytes compared with the effect of MIA alone using histological analysis. According to our data the impairment of motor function was less pronounced in the rat groups receiving intraarticular PACAP treatment. Our thermometric investigations revealed that PACAP co-administration significantly reduces joint temperature compared with MIA alone even after 4-week long investigation period. Our preliminary results suggested that intraarticular PACAP administration may exert cytoprotective effect inside hyaline articular cartilage layer by reducing deleterious influence of MIA on chondrocytes, and may have simultaneously an ameliorating effect in rat osteoarthritis. Additional studies must be performed to gain insight into the possible therapeutic involvement of PACAP in osteoarthritis pathophysiology.