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application/pdf, Journal Article, 関節リウマチを含む関節炎の症状改善を目的にコラーゲンペプチドが用いられているが、その有効性については未だ明確にされていない。消化されたコラーゲンペプチドの一部はペプチド態のまま血中に移行することから、本研究では、コラーゲン誘導性関節炎モデルであるDBA/1J マウスにニワトリI 型コラーゲン由来のコラーゲンペプチドあるいはそれと同組成のアミノ酸を摂取させて比較検討することにより、ペプチド態としてのコラーゲンペプチドの有効性を検討した。1日あたり100 mg のI 型コラーゲンペプチドあるいはそれと同じ組成のアミノ酸を経口投与することにより、関節での炎症がより強く生じた。関節炎スコア評価ではコラーゲンペプチドの関節炎軽減作用はみられず、関節軟骨におけるマトリックスメタロプロテアーゼ3（MMP3）遺伝子発現量の比較でもコラーゲンペプチド投与による有意な変化はみられなかった。一方、アミノ酸投与群では比較的早期から関節炎を発症した上に、マトリックス分解酵素であるMMP13 の発現量が有意に増加しており、コラーゲンペプチドと同組成のアミノ酸の投与により重症化する可能性が示唆された。I 型コラーゲンペプチド配合の健康食品は多く販売されているが、場合によってはその摂取が逆効果となる可能性があり、注意が必要であるものと考えられる。, Supplementation of gelatin or collagen peptides has been used to reduce the symptoms of inflammatory arthritis including rheumatoid arthritis, but the efficacy remains uncertain. It is known that ingested collagen peptides are absorbed partly in the form of bioactive peptides. In the present study, we investigated whether the effects of collagen peptide on inflammatory arthritis are due to its bioactive peptide in comparison with its constituent amino acids using DBA/1J mice. Unexpectedly, administration of daily 100 mg of collagen peptide derived from chicken type I collagen (i.e., collagen peptide group) or its constituent amino acids (i.e., amino acid group) rather stimulated collagen-induced arthritis in the DBA/1J mice. No significant difference was observed between amino acid and collagen peptide groups regarding either arthritis score or gene expression of matrix metalloprotease 3 (MMP3), a marker of synovial inflammation. Further, mice in the amino acid group developed arthritis relatively early stage and showed significantly higher expression of MMP13 as compared to those in other group mice, indicating administration of collagen-constituent amino acids possibly promoted the onset of arthritis inflammation in the DBA/1J mice. Many supplements contain gelatin or collagen peptide derived from type I collagen. These results raise a possibility that type I collagen peptide or its constituent amino acid may worsen inflammatory arthritis under some conditions.

I型コラーゲンは骨や結合組織,象牙質に豊富に含まれる線維状タンパクである。I型コラーゲンC-プロペプチドはコラーゲン分子への変換に伴って産生され,コラーゲン分子の会合とコラーゲン線維形成にとって必須である。近年,C-プロペプチド単体に様々な作用があることが報告され,特にin vitroにおいて硬組織形成に関与する前駆細胞の分化に抑制的に働くことが報告されている。つまり,硬組織の発達・形成過程での重要性が示されているが,in vivoにおけるC-プロペプチドの局在については明らかとなっていない。本研究では,抗I型コラーゲンC-プロペプチド抗体を用いた免疫組織染色を行い,骨および象牙質,セメント質といった硬組織領域における,それぞれの発現局在について調べ,抗I型コラーゲン抗体を用いたIHCとプロコラーゲンα2(I)鎖のcRNAプローブを用いたin situ hybridizationの結果と比較検討した。胎生期における下顎骨発生,および歯牙の発生過程におけるC-プロペプチドの局在から,骨,象牙質およびセメント質の活発な形成時期にはその基質において集積が認められた。くわえて,ヘルトウィッヒ上皮鞘周囲に認められたI型コラーゲンC-プロペプチドの集積の所見からも,すでに報告されている分化調節機構が骨組織のみならず,象牙質やセメント質の発達過程においても重要である可能性が示された。, Type I collagen is most commonly existing protein in mammals and particularly abundant in bone, dentin and connective tissues. The C-propeptide is produced while procollagen molecules which are composed of three pro-αchains are assembled to a collagen fibril. It has been suggested that the C-propeptide plays a role to regulate cell differentiation of osteoblasts. However, there is no information about localization in vivo of the C-propeptide in bone and other mineralized tissues such as dentin and cementum. In order to localize the C-propeptide in the mineralized tissues, the present study was designed to investigate their mineralizing processes with immunohistochemistry for the C-propeptide and the type I collagen fibril and with in situ hybridization for the procollagen. Anti-C-propeptide antibody stained the matrix-forming region in osteogenesis, dentinogenesis and cementogenesis. In particular, we found the immunoreactivity around Hertwig's epithelial sheath. The localization of the C-propeptide in vivo may be involved in function to modify cell differentiation on bone tissue and other mineralized tissues as dentin and cementum.

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Despite the diverse initial causes, chronic renal disease that progress to end-stage renal failure is a remarkably monotonous process that is characterized by the relentless accumulation of extracellular matrix (ECM) leading to widespread interstitial fibrosis. Hepatocyte growth factor (HGF), originally identified and cloned as a potent mitogen for hepatocyte, shows mitogenic, morphogenic and anti-apoptotic activities for a wide variety of cells including renal tubular epithelial cells. And HGF has been demonstrated to attenuate acute tubular necrosis and interstitial fibrosis in some of rodent models of kidney disease. But the mechanism of anti-fibrotic effects of HGF has been poorly understood in detail. Then, using HGF transgenic mice, we investigated how HGF could affect chronic toxic nephropathy/interstitial fibrosis caused by a nephrotoxin, aristrochic acid (AA). To find out molecular mechanisms of anti-fibrotic effects of HGF, cultured murine tubular epithelial cells (mProx24) were also employed. Significant tubular degeneration was observed both in the transgenic and the wild-type mice to the same degree after 2 week's treatment with AA. Interstitial fibrosis subsequently developed in the wild-type mice 4 weeks after cessation of AA administration. However, the transgenic mice manifested less fibrotic changes. Decreased expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) could partially account for the attenuation of fibrogenesis in the transgenic mouse kidney. HGF at 10 ng/mL and 100 ng/mL could block TIMP-1 gene expression in mProx24 induced by epidermal growth factor (EGF), but a decrease in the number of mProx24 via apoptosis induced by AA was blocked only by HGF at 100 ng/mL. In conclusion, circulating transgene-derived HGF (2～10 ng/mL) could not prevent tubular degeneration caused by AA, but facilitate its regeneration without significant fibrogenesis. These findings suggest possible therapeutic efficacy for renal interstitial fibrosis following tubular degeneration even of low-dose HGF.

Three-dimensional culture was performed using gamma-irradiated type Ⅰ collagen gel prepared from rat tail tendon. The morphological outgrowing appearance with in type Ⅰ collagen gel provided a marked difference in accordance with histopathological diagnosis, subsequently suggesting the difference in adhesion ability to type Ⅰ collagen. On the other hand, type Ⅰ collagen may be involved in differentiation-related proteins expressed during in vitro morphogenesis, such as carcinoembryonic antigen for tubulogenesis of the salivary gland. The present experiment system would be useful for studying further the relation between type Ⅰ collagen matrix and metastatic potentiality and/or cellular differentiation.