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IGFBP-5 Metabolism Is Disrupted in the Rat Medial Meniscal Tear Model of Osteoarthritis.

Yates MP, Settle SL, Yocum SA, Aggarwal P, Vickery LE, Aguiar DJ, Skepner AP, Kellner D, Weinrich SL, Sverdrup FM - Cartilage (2010)

Bottom Line: This activity was stimulated by calcium and was sensitive to serine protease inhibitors as well as peptide PB-145.Inhibition of IGFBP-5 proteolysis protected cartilage from lesion development and enhanced cartilage turnover.These data are consistent with IGFBP-5 playing a positive role in anabolic IGF signaling in cartilage.

View Article: PubMed Central - PubMed

Affiliation: Pfizer Global Research and Development, Chesterfield, Missouri.

ABSTRACT
Insulin-like growth factor binding protein 5 (IGFBP-5) has been proposed to promote cartilage anabolism through insulin-like growth factor (IGF-1) signaling. A proteolytic activity towards IGFBP-5 has been detected in synovial fluids from human osteoarthritic (OA) joints. The purpose of this study was to determine if protease activity towards IGFBP-5 is present in the rat medial meniscal tear (MMT) model of OA and whether inhibition of this activity would alter disease progression. Sprague-Dawley rats were subject to MMT surgery. Synovial fluid lavages were assessed for the presence of IGFBP-5 proteolytic activity. Treatment animals received intra-articular injections of vehicle or protease inhibitor peptide PB-145. Cartilage lesions were monitored by India ink staining followed by macroscopic measurement of lesion width and depth. The MMT surgery induced a proteolytic activity towards IGFPB-5 that was detectable in joint fluid. This activity was stimulated by calcium and was sensitive to serine protease inhibitors as well as peptide PB-145. Significantly, intra-articular administration of PB-145 after surgery protected cartilage from lesion development. PB-145 treatment also resulted in an increase in cartilage turnover as evidenced by increases in serum levels of procollagen type II C-propeptide (CPII) as well as synovial fluid lavage levels of collagen type II neoepitope (TIINE). IGFBP-5 metabolism is disrupted in the rat MMT model of OA, potentially contributing to cartilage degradation. Inhibition of IGFBP-5 proteolysis protected cartilage from lesion development and enhanced cartilage turnover. These data are consistent with IGFBP-5 playing a positive role in anabolic IGF signaling in cartilage.

No MeSH data available.


Related in: MedlinePlus

Biomarkers of cartilage turnover. (A) Synovial fluid lavage levels of type II collagen neoepitope (TIINE). High-dose PB-145 (500 ug) was different than vehicle based on a 2-sided t test for independent samples. (B) Serum levels of collagen II C-propeptide (CPII). See Methods section for details.
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fig7-1947603509359189: Biomarkers of cartilage turnover. (A) Synovial fluid lavage levels of type II collagen neoepitope (TIINE). High-dose PB-145 (500 ug) was different than vehicle based on a 2-sided t test for independent samples. (B) Serum levels of collagen II C-propeptide (CPII). See Methods section for details.

Mentions: All values are presented as mean ± standard deviation (except Fig. 7A, mean ± standard error of the mean). Statistical analyses are based on a 1- or 2-sided t test for independent samples as indicated in figure legends.


IGFBP-5 Metabolism Is Disrupted in the Rat Medial Meniscal Tear Model of Osteoarthritis.

Yates MP, Settle SL, Yocum SA, Aggarwal P, Vickery LE, Aguiar DJ, Skepner AP, Kellner D, Weinrich SL, Sverdrup FM - Cartilage (2010)

Biomarkers of cartilage turnover. (A) Synovial fluid lavage levels of type II collagen neoepitope (TIINE). High-dose PB-145 (500 ug) was different than vehicle based on a 2-sided t test for independent samples. (B) Serum levels of collagen II C-propeptide (CPII). See Methods section for details.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4440612&req=5

fig7-1947603509359189: Biomarkers of cartilage turnover. (A) Synovial fluid lavage levels of type II collagen neoepitope (TIINE). High-dose PB-145 (500 ug) was different than vehicle based on a 2-sided t test for independent samples. (B) Serum levels of collagen II C-propeptide (CPII). See Methods section for details.
Mentions: All values are presented as mean ± standard deviation (except Fig. 7A, mean ± standard error of the mean). Statistical analyses are based on a 1- or 2-sided t test for independent samples as indicated in figure legends.

Bottom Line: This activity was stimulated by calcium and was sensitive to serine protease inhibitors as well as peptide PB-145.Inhibition of IGFBP-5 proteolysis protected cartilage from lesion development and enhanced cartilage turnover.These data are consistent with IGFBP-5 playing a positive role in anabolic IGF signaling in cartilage.

View Article: PubMed Central - PubMed

Affiliation: Pfizer Global Research and Development, Chesterfield, Missouri.

ABSTRACT
Insulin-like growth factor binding protein 5 (IGFBP-5) has been proposed to promote cartilage anabolism through insulin-like growth factor (IGF-1) signaling. A proteolytic activity towards IGFBP-5 has been detected in synovial fluids from human osteoarthritic (OA) joints. The purpose of this study was to determine if protease activity towards IGFBP-5 is present in the rat medial meniscal tear (MMT) model of OA and whether inhibition of this activity would alter disease progression. Sprague-Dawley rats were subject to MMT surgery. Synovial fluid lavages were assessed for the presence of IGFBP-5 proteolytic activity. Treatment animals received intra-articular injections of vehicle or protease inhibitor peptide PB-145. Cartilage lesions were monitored by India ink staining followed by macroscopic measurement of lesion width and depth. The MMT surgery induced a proteolytic activity towards IGFPB-5 that was detectable in joint fluid. This activity was stimulated by calcium and was sensitive to serine protease inhibitors as well as peptide PB-145. Significantly, intra-articular administration of PB-145 after surgery protected cartilage from lesion development. PB-145 treatment also resulted in an increase in cartilage turnover as evidenced by increases in serum levels of procollagen type II C-propeptide (CPII) as well as synovial fluid lavage levels of collagen type II neoepitope (TIINE). IGFBP-5 metabolism is disrupted in the rat MMT model of OA, potentially contributing to cartilage degradation. Inhibition of IGFBP-5 proteolysis protected cartilage from lesion development and enhanced cartilage turnover. These data are consistent with IGFBP-5 playing a positive role in anabolic IGF signaling in cartilage.

No MeSH data available.


Related in: MedlinePlus