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CK2.1, a bone morphogenetic protein receptor type Ia mimetic peptide, repairs cartilage in mice with destabilized medial meniscus
BACKGROUND: Osteoarthritis (OA) of the knee involves degeneration of articular cartilage of the diarthrodial joints. Current treatment options temporarily relieve the joint pain but do not restore the lost cartilage. We recently designed a novel bone morphogenetic protein receptor type I (BMPRI) mim...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5395786/ https://www.ncbi.nlm.nih.gov/pubmed/28420447 http://dx.doi.org/10.1186/s13287-017-0537-y |
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author | Akkiraju, Hemanth Srinivasan, Padma Pradeepa Xu, Xian Jia, Xinqiao Safran, Catherine B. Kirn Nohe, Anja |
author_facet | Akkiraju, Hemanth Srinivasan, Padma Pradeepa Xu, Xian Jia, Xinqiao Safran, Catherine B. Kirn Nohe, Anja |
author_sort | Akkiraju, Hemanth |
collection | PubMed |
description | BACKGROUND: Osteoarthritis (OA) of the knee involves degeneration of articular cartilage of the diarthrodial joints. Current treatment options temporarily relieve the joint pain but do not restore the lost cartilage. We recently designed a novel bone morphogenetic protein receptor type I (BMPRI) mimetic peptide, CK2.1, that activates BMPRIa signaling in the absence of bone morphogenetic protein (BMP). Our previous research demonstrated that CK2.1 induced chondrogenesis in vitro and in vivo; however, it is unknown if CK2.1 restores damaged articular cartilage in vivo. In this study, we demonstrate that CK2.1 induced articular cartilage (AC) repair in an OA mouse model. METHODS: We designed hyaluronic acid (HA)-based hydrogel particles (HGPs) that slowly release CK2.1. HGP-CK2.1 particles were tested for chondrogenic potency on pluripotent mesenchymal stem cells (C3H10T1/2 cells) and locally injected into the intra-articular capsule in mice with cartilage defects. C57BL/6J mice were operated on to destabilize the medial meniscus and these mice were kept for 6 weeks after surgery to sustain OA-like damage. Mice were then injected via the intra-articular capsule with HGP-CK2.1; 4 weeks after injection the mice were sacrificed and their femurs were analyzed for cartilage defects. RESULTS: Immunohistochemical analysis of the cartilage demonstrated complete repair of the AC compared to sham-operated mice. Immunofluorescence analysis revealed collagen type IX production along with collagen type II in the AC of mice injected with HGP-CK2.1. Mice injected with phosphate-buffered saline (PBS) and HGP alone had greater collagen type X and osteocalcin production, in sharp contrast to those injected with HGP-CK2.1, indicating increased chondrocyte hypertrophy. CONCLUSIONS: Our results demonstrate that the slow release HGP-CK2.1 drives cartilage repair without the induction of chondrocyte hypertrophy. The peptide CK2.1 could be a powerful tool in understanding the signaling pathways contributing to the repair process, and also may be used as a potential therapeutic for treating degenerative cartilage diseases such as OA. |
format | Online Article Text |
id | pubmed-5395786 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-53957862017-04-20 CK2.1, a bone morphogenetic protein receptor type Ia mimetic peptide, repairs cartilage in mice with destabilized medial meniscus Akkiraju, Hemanth Srinivasan, Padma Pradeepa Xu, Xian Jia, Xinqiao Safran, Catherine B. Kirn Nohe, Anja Stem Cell Res Ther Research BACKGROUND: Osteoarthritis (OA) of the knee involves degeneration of articular cartilage of the diarthrodial joints. Current treatment options temporarily relieve the joint pain but do not restore the lost cartilage. We recently designed a novel bone morphogenetic protein receptor type I (BMPRI) mimetic peptide, CK2.1, that activates BMPRIa signaling in the absence of bone morphogenetic protein (BMP). Our previous research demonstrated that CK2.1 induced chondrogenesis in vitro and in vivo; however, it is unknown if CK2.1 restores damaged articular cartilage in vivo. In this study, we demonstrate that CK2.1 induced articular cartilage (AC) repair in an OA mouse model. METHODS: We designed hyaluronic acid (HA)-based hydrogel particles (HGPs) that slowly release CK2.1. HGP-CK2.1 particles were tested for chondrogenic potency on pluripotent mesenchymal stem cells (C3H10T1/2 cells) and locally injected into the intra-articular capsule in mice with cartilage defects. C57BL/6J mice were operated on to destabilize the medial meniscus and these mice were kept for 6 weeks after surgery to sustain OA-like damage. Mice were then injected via the intra-articular capsule with HGP-CK2.1; 4 weeks after injection the mice were sacrificed and their femurs were analyzed for cartilage defects. RESULTS: Immunohistochemical analysis of the cartilage demonstrated complete repair of the AC compared to sham-operated mice. Immunofluorescence analysis revealed collagen type IX production along with collagen type II in the AC of mice injected with HGP-CK2.1. Mice injected with phosphate-buffered saline (PBS) and HGP alone had greater collagen type X and osteocalcin production, in sharp contrast to those injected with HGP-CK2.1, indicating increased chondrocyte hypertrophy. CONCLUSIONS: Our results demonstrate that the slow release HGP-CK2.1 drives cartilage repair without the induction of chondrocyte hypertrophy. The peptide CK2.1 could be a powerful tool in understanding the signaling pathways contributing to the repair process, and also may be used as a potential therapeutic for treating degenerative cartilage diseases such as OA. BioMed Central 2017-04-18 /pmc/articles/PMC5395786/ /pubmed/28420447 http://dx.doi.org/10.1186/s13287-017-0537-y Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. 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 Akkiraju, Hemanth Srinivasan, Padma Pradeepa Xu, Xian Jia, Xinqiao Safran, Catherine B. Kirn Nohe, Anja CK2.1, a bone morphogenetic protein receptor type Ia mimetic peptide, repairs cartilage in mice with destabilized medial meniscus |
title | CK2.1, a bone morphogenetic protein receptor type Ia mimetic peptide, repairs cartilage in mice with destabilized medial meniscus |
title_full | CK2.1, a bone morphogenetic protein receptor type Ia mimetic peptide, repairs cartilage in mice with destabilized medial meniscus |
title_fullStr | CK2.1, a bone morphogenetic protein receptor type Ia mimetic peptide, repairs cartilage in mice with destabilized medial meniscus |
title_full_unstemmed | CK2.1, a bone morphogenetic protein receptor type Ia mimetic peptide, repairs cartilage in mice with destabilized medial meniscus |
title_short | CK2.1, a bone morphogenetic protein receptor type Ia mimetic peptide, repairs cartilage in mice with destabilized medial meniscus |
title_sort | ck2.1, a bone morphogenetic protein receptor type ia mimetic peptide, repairs cartilage in mice with destabilized medial meniscus |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5395786/ https://www.ncbi.nlm.nih.gov/pubmed/28420447 http://dx.doi.org/10.1186/s13287-017-0537-y |
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