Effects of chronic growth hormone and insulin‐like growth factor 1 deficiency on osteoarthritis severity in rat knee joints

Abstract

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.Conclusion. 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.

Proinflammatory Actions of Visfatin/Nicotinamide Phosphoribosyltransferase (Nampt) Involve Regulation of Insulin Signaling Pathway and Nampt Enzymatic Activity

“…Therefore, binding of visfatin to GHR should be tested in articular chondrocytes. Interestingly, GH/IGF-1 deficiency causes an increased severity of articular cartilage lesions of OA (37). Thus, if visfatin binds to GHR, it may decrease GH binding to GHR, possibly leading to an increased OA severity in accord with the capacity of visfatin to increase PGE 2 release in articular chondrocytes.…”

Biochemical Mediators Involved in Cartilage Degradation and the Induction of Pain in Osteoarthritis

“…In vitro, IGF-1 induces anabolic and anti-catabolic effects in normal articular cartilage from a variety of species (53,175). In vivo studies support in vitro findings, as IGF-1 deficiency in rats leads to the development of articular cartilage lesions (176). In animal models, IGF-1 enhances repair of extensive cartilage defects and protects synovial membrane tissue from chronic inflammation (177,178).…”

IGF-1 deficiency in a critical period early in life influences the vascular aging phenotype in mice by altering miRNA-mediated post-transcriptional gene regulation: implications for the developmental origins of health and disease hypothesis

“…Additionally, rodent models with developmental IGF-1 deficiency exhibit organ-specific signs of accelerated aging in the central nervous system and the musculoskeletal system (Ekenstedt et al 2006;Sonntag et al 2013). Vascular endothelial and smooth muscle cells abundantly express IGF1R and are more sensitive to IGF-1 than to insulin (Chisalita and Arnqvist 2004;Chisalita et al 2009;Johansson et al 2008).…”