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The disease-modifying effect of dehydroepiandrosterone in different stages of experimentally induced osteoarthritis: a histomorphometric study

BACKGROUND: Osteoarthritis (OA) is likely to become an increasing burden in the coming decades. Various agents have been developed to slow the progression of OA, and are collectively known as ‘disease-modifying drugs’, however, there is still little reliable evidence that such agents will be success...

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Autores principales: Huang, Kai, Bao, Jia-peng, Jennings, Gavin James, Wu, Li-dong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4521359/
https://www.ncbi.nlm.nih.gov/pubmed/26228537
http://dx.doi.org/10.1186/s12891-015-0595-1
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author Huang, Kai
Bao, Jia-peng
Jennings, Gavin James
Wu, Li-dong
author_facet Huang, Kai
Bao, Jia-peng
Jennings, Gavin James
Wu, Li-dong
author_sort Huang, Kai
collection PubMed
description BACKGROUND: Osteoarthritis (OA) is likely to become an increasing burden in the coming decades. Various agents have been developed to slow the progression of OA, and are collectively known as ‘disease-modifying drugs’, however, there is still little reliable evidence that such agents will be successful. Dehydroepiandrosterone (DHEA), a sex hormone precursor, has been recently proven as protective agent against OA, but the exact mechanism is still unkown. In the current study, the effects of weekly intra-articular injections of DHEA in preventing the progression of existing cartilage degeneration in an OA rabbit model were evaluated. The aim of the current study is to demonstrate the feature of its disease-modifying efficacy during OA progression. METHODS: Thirty male New Zealand white rabbits were used in this study. An anterior cruciate ligament transection (ACLT) model was used to create a progressive OA model in twenty rabbits. The animals were treated with DHEA or a placebo and were necropsied at 9 and 16 weeks. Ten rabbits receiving sham operations served as controls. The articular cartilage of the medial femoral condyle (MFC), lateral femoral condyle (LFC), medial tibial plateau (MTP) and lateral tibial plateau (LTP) was evaluated macroscopically and histologically. RESULTS: In the joints of the sham-operated rabbits, few histological changes were detected on the articular surfaces of the femoral condyles and tibial plateaus. ACLT obviously induced erosive changes on the cartilage surfaces. Compared to the placebo group, the macroscopic and Mankin score analyses demonstrated that the DHEA treatment markedly reduced the cartilage lesions and delayed cartilage degeneration in the four regions of the knee at 9 weeks after operation (macroscopic score: MFC P = 0.013; LFC P = 0.048; MTP P = 0.045; LTP P = 0.02, Mankin score: MFC P = 0.012; LFC P = 0.034; MTP P = 0.016; LTP P = 0.002). At 16 weeks, DHEA demonstrated chondroprotective effects on the lateral compartment of the knee compared to the placebo group, whereas the cartilage degeneration at the medial compartment of the knee did not differ among the groups (macroscopic score: LFC P = 0.046; LTP = 0.034, Mankin score: LFC P = 0.005; LTP P = 0.002). CONCLUSION: The disease-modifying efficacy of DHEA aganist OA is time-specific and site-dependent. DHEA could be used as a disease-modifying strategy to limit the progression of OA, especially in the middle stage.
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spelling pubmed-45213592015-08-01 The disease-modifying effect of dehydroepiandrosterone in different stages of experimentally induced osteoarthritis: a histomorphometric study Huang, Kai Bao, Jia-peng Jennings, Gavin James Wu, Li-dong BMC Musculoskelet Disord Research Article BACKGROUND: Osteoarthritis (OA) is likely to become an increasing burden in the coming decades. Various agents have been developed to slow the progression of OA, and are collectively known as ‘disease-modifying drugs’, however, there is still little reliable evidence that such agents will be successful. Dehydroepiandrosterone (DHEA), a sex hormone precursor, has been recently proven as protective agent against OA, but the exact mechanism is still unkown. In the current study, the effects of weekly intra-articular injections of DHEA in preventing the progression of existing cartilage degeneration in an OA rabbit model were evaluated. The aim of the current study is to demonstrate the feature of its disease-modifying efficacy during OA progression. METHODS: Thirty male New Zealand white rabbits were used in this study. An anterior cruciate ligament transection (ACLT) model was used to create a progressive OA model in twenty rabbits. The animals were treated with DHEA or a placebo and were necropsied at 9 and 16 weeks. Ten rabbits receiving sham operations served as controls. The articular cartilage of the medial femoral condyle (MFC), lateral femoral condyle (LFC), medial tibial plateau (MTP) and lateral tibial plateau (LTP) was evaluated macroscopically and histologically. RESULTS: In the joints of the sham-operated rabbits, few histological changes were detected on the articular surfaces of the femoral condyles and tibial plateaus. ACLT obviously induced erosive changes on the cartilage surfaces. Compared to the placebo group, the macroscopic and Mankin score analyses demonstrated that the DHEA treatment markedly reduced the cartilage lesions and delayed cartilage degeneration in the four regions of the knee at 9 weeks after operation (macroscopic score: MFC P = 0.013; LFC P = 0.048; MTP P = 0.045; LTP P = 0.02, Mankin score: MFC P = 0.012; LFC P = 0.034; MTP P = 0.016; LTP P = 0.002). At 16 weeks, DHEA demonstrated chondroprotective effects on the lateral compartment of the knee compared to the placebo group, whereas the cartilage degeneration at the medial compartment of the knee did not differ among the groups (macroscopic score: LFC P = 0.046; LTP = 0.034, Mankin score: LFC P = 0.005; LTP P = 0.002). CONCLUSION: The disease-modifying efficacy of DHEA aganist OA is time-specific and site-dependent. DHEA could be used as a disease-modifying strategy to limit the progression of OA, especially in the middle stage. BioMed Central 2015-07-31 /pmc/articles/PMC4521359/ /pubmed/26228537 http://dx.doi.org/10.1186/s12891-015-0595-1 Text en © Huang et al. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Huang, Kai
Bao, Jia-peng
Jennings, Gavin James
Wu, Li-dong
The disease-modifying effect of dehydroepiandrosterone in different stages of experimentally induced osteoarthritis: a histomorphometric study
title The disease-modifying effect of dehydroepiandrosterone in different stages of experimentally induced osteoarthritis: a histomorphometric study
title_full The disease-modifying effect of dehydroepiandrosterone in different stages of experimentally induced osteoarthritis: a histomorphometric study
title_fullStr The disease-modifying effect of dehydroepiandrosterone in different stages of experimentally induced osteoarthritis: a histomorphometric study
title_full_unstemmed The disease-modifying effect of dehydroepiandrosterone in different stages of experimentally induced osteoarthritis: a histomorphometric study
title_short The disease-modifying effect of dehydroepiandrosterone in different stages of experimentally induced osteoarthritis: a histomorphometric study
title_sort disease-modifying effect of dehydroepiandrosterone in different stages of experimentally induced osteoarthritis: a histomorphometric study
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4521359/
https://www.ncbi.nlm.nih.gov/pubmed/26228537
http://dx.doi.org/10.1186/s12891-015-0595-1
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