Gene expression profile of the cartilage tissue spontaneously regenerated in vivo by using a novel double-network gel: Comparisons with the normal articular cartilage

Ryusei Imabuchi,Takayuki Kurokawa,Jian Ping Gong,Nobuto Kitamura,Kazunori Yasuda,Shin Onodera,Yoshihiro Ohmiya,Hyuck Joon Kwon

doi:10.1186/1471-2474-12-213

Ryusei Imabuchi, Takayuki Kurokawa + Show 6 more

Open Access

https://doi.org/10.1186/1471-2474-12-213

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Abstract

BackgroundWe have recently found a phenomenon that spontaneous regeneration of a hyaline cartilage-like tissue can be induced in a large osteochondral defect by implanting a double-network (DN) hydrogel plug, which was composed of poly-(2-Acrylamido-2-methylpropanesulfonic acid) and poly-(N, N'-Dimetyl acrylamide), at the bottom of the defect. The purpose of this study was to clarify gene expression profile of the regenerated tissue in comparison with that of the normal articular cartilage.MethodsWe created a cylindrical osteochondral defect in the rabbit femoral grooves. Then, we implanted the DN gel plug at the bottom of the defect. At 2 and 4 weeks after surgery, the regenerated tissue was analyzed using DNA microarray and immunohistochemical examinations.ResultsThe gene expression profiles of the regenerated tissues were macroscopically similar to the normal cartilage, but showed some minor differences. The expression degree of COL2A1, COL1A2, COL10A1, DCN, FMOD, SPARC, FLOD2, CHAD, CTGF, and COMP genes was greater in the regenerated tissue than in the normal cartilage. The top 30 genes that expressed 5 times or more in the regenerated tissue as compared with the normal cartilage included type-2 collagen, type-10 collagen, FN, vimentin, COMP, EF1alpha, TFCP2, and GAPDH genes.ConclusionsThe tissue regenerated by using the DN gel was genetically similar but not completely identical to articular cartilage. The genetic data shown in this study are useful for future studies to identify specific genes involved in spontaneous cartilage regeneration.

Highlights

We have recently found a phenomenon that spontaneous regeneration of a hyaline cartilage-like tissue can be induced in a large osteochondral defect by implanting a double-network (DN) hydrogel plug, which was composed of poly-(2-Acrylamido-2-methylpropanesulfonic acid) and poly-(N, N’-Dimetyl acrylamide), at the bottom of the defect
The present study showed that gene expression profiles of the tissues spontaneously regenerated at both 2 and 4 weeks by using the poly-(2-Acrylamido-2-methylpropanesulfonic acid) (PAMPS)/PDMAAm DN gel were similar to the normal cartilage
We found that Transcription Factor CP2 (TFCP2), CITED, and elongation factor-1 (EF-1) alpha were highly expressed in the cartilage tissue regenerated by the DN gel implantation in comparison to the normal cartilage

Summary

Introduction

We have recently found a phenomenon that spontaneous regeneration of a hyaline cartilage-like tissue can be induced in a large osteochondral defect by implanting a double-network (DN) hydrogel plug, which was composed of poly-(2-Acrylamido-2-methylpropanesulfonic acid) and poly-(N, N’-Dimetyl acrylamide), at the bottom of the defect. Articular cartilage is frequently damaged due to trauma, and treatment of damaged cartilage is a significant health care concern It has been a common belief up to now that hyaline cartilage tissue cannot spontaneously regenerate in vivo [2,3]. We have considered that, if we implant any bioactive elastic hydrogel at the bottom of an osteochondral defect under conditions similar to in the above-described multiple-penetration surgery, we may be able to induce hyaline cartilage regeneration in vivo in the defect space. The PAMPS/PDMAAm DN gel surface can enhance differentiation of chondrogenic ATDC5 cells into chondrocytes in the in vitro condition [21,22]

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