Effects of chronic growth hormone and insulin-like growth factor 1 deficiency on osteoarthritis severity in rat knee joints.
OBJECTIVE
To determine the effects of chronic deficiency of growth hormone (GH) and insulin-like growth factor 1 (IGF-1) on osteoarthritis (OA) severity.


METHODS
Thirty-five rats were divided into 4 treatment groups at 4 weeks of age: 1 control group (normal GH/IGF-1 levels [heterozygous]) and 3 groups of dwarves with a genetic mutation that results in GH deficiency. The first dwarf group received GH for 64 weeks (GH replete) and the second received GH until 14 weeks of age, followed by saline for 50 weeks (adult-onset GH/IGF-1 deficiency [AO-GHD]). The third dwarf group received saline injections only (lifetime GH deficient [GHD]). Sections of the medial knee joint compartment were graded and measured histologically; data were summarized using factor analysis, and treatment effects were assessed using analysis of variance and adjusting for body weight.


RESULTS
Terminal IGF-1 levels and body weights were significantly affected by treatment (P = 0.002 and P < 0.001, respectively). Factor analysis yielded a total of 5 factors, the first 3 of which were not significantly affected by treatment. Factor 4 (weighted by medial tibial plateau articular cartilage width and area) was significantly affected by treatment (P < 0.012), with larger values in the AO-GHD group than in the GHD group (P < 0.05). Factor 5 (weighted primarily by articular cartilage structure and loss of toluidine blue staining scores) also was significantly affected by treatment (P < 0.001), and was significantly lower (less severe lesions) in the GH replete group than in all other treatment groups (P < 0.05). Despite the presence of cartilage lesions, osteophytes and subchondral sclerosis were not observed in GH/IGF-1-deficient animals.


CONCLUSIONS
These results indicate that chronic GH/IGF-1 deficiency causes an increased severity of articular cartilage lesions of OA without the bony lesions normally seen in this disease.
Ekenstedt
Kari J
KJ
Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, MN 55108, USA. eken0003@umn.edu
Sonntag
William E
WE
Loeser
Richard F
RF
Lindgren
Bruce R
BR
Carlson
Cathy S
CS
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002358:Cartilage, Articular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D013006:Growth Hormone / Q000172:deficiency* / Q000235:genetics / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D008297:Male; D020370:Osteoarthritis, Knee / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D011917:Rats, Inbred Lew; D011922:Rats, Mutant Strains; D013264:Stifle / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology
D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone