TY - JOUR
T1 - Identification and characterization of insulin-like growth factors (IGFs), IGF-binding proteins (IGFBPs), and IGFBP proteases in human synovial fluid
AU - Matsumoto, Tomoko
AU - Gargosky, Sharron E.
AU - Iwasaki, Katsuro
AU - Rosenfeld, Ron G.
N1 - Copyright:
Copyright 2007 Elsevier B.V., All rights reserved.
PY - 1996
Y1 - 1996
N2 - The insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) in human synovial fluid play an important role in maintaining articular cartilage metabolism. In this study we measured the concentrations of IGF-I, IGF-II, and IGFBP-3 in normal human synovial fluid by RIA and characterized the IGFBPs by Western ligand blot (WLB), Western immunoblot, and immunoprecipitation. We also extended the study and compared normal synovial fluid to synovial fluids from patients with osteoarthritis (OA) and rheumatoid arthritis (RA). The concentrations of IGF-I, IGF-II, and IGFBP-3 in normal synovial fluid were 19 ± 3 (mean ± SE), 194 ± 14, and 349 ± 65 ng/mL, respectively. In synovial fluid of patients with OA, IGF-I levels were elevated, whereas IGF-II was decreased, and the IGFBP-3 level was similar to the control value. In patients with RA, both IGF-I and IGFBP-3 were elevated, whereas IGF-II remained unchanged. WLB and immunoprecipitation of normal synovial fluid revealed IGFBP-1 (26-29 kDa), IGFBP-2 (32 kDa), IGFBP-3 (42- to 39-kDa doublet), and IGFBP-4 (24 kDa); the IGFBP-3 doublet was very faint. In RA synovial fluid, all IGFBPs were dramatically increased, whereas little change was seen in the synovial fluid of OA. Western immunoblot against IGFBP-3 revealed a prominent 30-kDa immunoreactive fragment of IGFBP-3 in synovial fluids of normal adults as well as in those of RA and OA patients. This was concurrent with detect able IGFBP-3 protease activity, which was characterized to be of the metallo- and serine protease family. Thus, in normal synovial fluid, there is a balance of circulating IGF, IGFBP, and proteases to modulate the bioactivity of IGF. In pathological states, the increased IGF-I concentrations were accompanied by an increase in IGFBP-3 levels in synovial fluid. These findings suggest that alteration of the IGF and IGFBP axis in pathological states may be important for understanding the underling pathophysiology of disordered articular growth and metabolism.
AB - The insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) in human synovial fluid play an important role in maintaining articular cartilage metabolism. In this study we measured the concentrations of IGF-I, IGF-II, and IGFBP-3 in normal human synovial fluid by RIA and characterized the IGFBPs by Western ligand blot (WLB), Western immunoblot, and immunoprecipitation. We also extended the study and compared normal synovial fluid to synovial fluids from patients with osteoarthritis (OA) and rheumatoid arthritis (RA). The concentrations of IGF-I, IGF-II, and IGFBP-3 in normal synovial fluid were 19 ± 3 (mean ± SE), 194 ± 14, and 349 ± 65 ng/mL, respectively. In synovial fluid of patients with OA, IGF-I levels were elevated, whereas IGF-II was decreased, and the IGFBP-3 level was similar to the control value. In patients with RA, both IGF-I and IGFBP-3 were elevated, whereas IGF-II remained unchanged. WLB and immunoprecipitation of normal synovial fluid revealed IGFBP-1 (26-29 kDa), IGFBP-2 (32 kDa), IGFBP-3 (42- to 39-kDa doublet), and IGFBP-4 (24 kDa); the IGFBP-3 doublet was very faint. In RA synovial fluid, all IGFBPs were dramatically increased, whereas little change was seen in the synovial fluid of OA. Western immunoblot against IGFBP-3 revealed a prominent 30-kDa immunoreactive fragment of IGFBP-3 in synovial fluids of normal adults as well as in those of RA and OA patients. This was concurrent with detect able IGFBP-3 protease activity, which was characterized to be of the metallo- and serine protease family. Thus, in normal synovial fluid, there is a balance of circulating IGF, IGFBP, and proteases to modulate the bioactivity of IGF. In pathological states, the increased IGF-I concentrations were accompanied by an increase in IGFBP-3 levels in synovial fluid. These findings suggest that alteration of the IGF and IGFBP axis in pathological states may be important for understanding the underling pathophysiology of disordered articular growth and metabolism.
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U2 - 10.1210/jc.81.1.150
DO - 10.1210/jc.81.1.150
M3 - Article
C2 - 8550744
AN - SCOPUS:0030026363
SN - 0021-972X
VL - 81
SP - 150
EP - 155
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 1
ER -