Changes in the local regulation of insulin-like growth factors I and II and insulin-like growth factor-binding proteins in osteoarthritis of the canine stifle joint secondary to cruciate ligament rupture.

Fernihough JK, Innes JF, Billingham ME, Holly JM.

Academic Rheumatology, School of Comparative Morphology, Southwell Street,

Bristol; the Department of Veterinary Clinical Sciences, Small Animal Hospital, University of Liverpool, Liverpool; and the Department of Surgery, Bristol Royal Infirmary, Bristol, United Kingdom.

OBJECTIVES-To investigate changes in concentrations of insulin-like growth factors I (IGF-I) and II (IGF-II) and the expression of IGF-binding proteins (IGFBP) in synovial fluids from dogs with naturally occurring osteoarthritis (OA) of the canine stifle joint secondary to cranial cruciate ligament (CCL) rupture.

STUDY DESIGN-Prospective study with synovial fluid sampling from diseased and contralateral unaffected joints at 0, 1.5, and 5 months.

SAMPLE POPULATION-Eleven dogs with unilateral CCL deficiency, with unaffected contralateral joints.

METHODS-IGF-I and IGF-II concentrations in synovial fluids were estimated by radioimmunoassay at 0, 1.5, and 5 months; Western ligand blotting was performed for intact IGFBPs at 0, 1.5, 5, and 9 months. Both stifle joints were radiographed at 0, 7, and 13 months.

RESULTS-The IGF system is altered after CCL rupture and during development of early OA. Mean IGF-I and IGF-II concentrations in index stifle joints at study entry were 201.6 microg/mL and 345.7 microg/mL, respectively, compared with 57.7 microg/mL and 79.4 microg/mL, respectively, for contralateral joints. Index joint IGF concentrations increased after surgical treatment and then declined, although they remained higher than contralateral joints. Index joints had increases in IGFBP-3 and -4, and a decrease in IGFBP-2 expression compared with contralateral joints. CONCLUSIONS-Although IGF concentrations are increased in canine OA, alterations in IGFBP profiles may limit the tissue availability of IGF.

CLINICAL RELEVANCE-Manipulation of the IGF system may provide an opportunity for novel treatments of OA in dogs.