RRC ID 44714
著者 Ishihara T, Kakiya K, Takahashi K, Miwa H, Rokushima M, Yoshinaga T, Tanaka Y, Ito T, Togame H, Takemoto H, Amano M, Iwasaki N, Minami A, Nishimura S.
タイトル Discovery of novel differentiation markers in the early stage of chondrogenesis by glycoform-focused reverse proteomics and genomics.
ジャーナル Biochim Biophys Acta
Abstract BACKGROUND:Osteoarthritis (OA) is one of the most common chronic diseases among adults, especially the elderly, which is characterized by destruction of the articular cartilage. Despite affecting more than 100 million individuals all over the world, therapy is currently limited to treating pain, which is a principal symptom of OA. New approaches to the treatment of OA that induce regeneration and repair of cartilage are strongly needed.
METHODS:To discover potent markers for chondrogenic differentiation, glycoform-focused reverse proteomics and genomics were performed on the basis of glycoblotting-based comprehensive approach.
RESULTS:Expression levels of high-mannose type N-glycans were up-regulated significantly at the late stage of differentiation of the mouse chondroprogenitor cells. Among 246 glycoproteins carrying this glycotype identified by ConA affinity chromatography and LC/MS, it was demonstrated that 52% are classified as cell surface glycoproteins. Gene expression levels indicated that mRNAs for 15 glycoproteins increased distinctly in the earlier stages during differentiation compared with Type II collagen. The feasibility of mouse chondrocyte markers in human chondrogenesis model was demonstrated by testing gene expression levels of these 15 glycoproteins during differentiation in human mesenchymal stem cells.
CONCLUSION:The results showed clearly an evidence of up-regulation of 5 genes, ectonucleotide pyrophosphatase/phosphodiesterase family member 1, collagen alpha-1(III) chain, collagen alpha-1(XI) chain, aquaporin-1, and netrin receptor UNC5B, in the early stages of differentiation.
GENERAL SIGNIFICANCE:These cell surface 5 glycoproteins become highly sensitive differentiation markers of human chondrocytes that contribute to regenerative therapies, and development of novel therapeutic reagents.
巻・号 1840(1)
ページ 645-55
公開日 2014-1-1
DOI 10.1016/j.bbagen.2013.10.027
PII S0304-4165(13)00467-4
PMID 24161698
MeSH Adult Animals Antigens, Differentiation / metabolism* Cell Differentiation Cells, Cultured Chondrocytes / cytology* Chondrocytes / metabolism* Chondrogenesis / physiology* Gene Expression Profiling Genomics* Glycoproteins / genetics Glycoproteins / metabolism Humans Mesenchymal Stem Cells / cytology* Mesenchymal Stem Cells / metabolism Mice Oligonucleotide Array Sequence Analysis Polysaccharides / metabolism Proteomics* RNA, Messenger / genetics Real-Time Polymerase Chain Reaction Reverse Transcriptase Polymerase Chain Reaction
IF 3.411
引用数 9
WOS 分野 BIOPHYSICS BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
ヒト・動物細胞 ATDC5(RCB0565)