Effects of elcatonin on matrix calcification of Meckel\u27s cartilage in vitro

ウナギ由来のエルカトニン(ELC)は優れた薬理学的効能から実験的ないし臨床試験的改善薬として骨粗鬆症患者に投与され良好な成績が得られている。本実験では,胎生17日マウスメッケル軟骨に対するELCの効果を細胞培養と器官培養を用いて解析した。細胞培養と器官培養のためのメッケル軟骨は以下の4種類の培養液で最長4週間まで培養した。培養液として,培養液1;イーグル培地(α-MEM),培養液2;α-MEM+β-グリセロリン酸(β-Gly),培養液3;α-MEM+ELCと培養液4;α-MEM+β-Gly+ELCを用いた。試料はアルカリフォスファターゼ(ALPase)とbromodeoxyuridine (BrdU)の取り込みを含む組織学,組織化学的方法によって解析した。ELCを含む培養液は,より効果的に石灰化を誘導することがホン・コッサ染色によって示された。BrdUの取り込みによる細胞増殖率は,培養液1と3との間では有意差が認められなかった。ALPase活性は,基質の石灰化に先駆けて促進されることが細胞培養と器官培養での組織化学と蛍光免疫染色によって確認された。ELCはβ-Glyとほぼ同等量のALPaseを発現し,さらにELCとβ-Glyを含む培養液4では相乗的にALPase活性と石灰化を誘導した。本研究の結果から,ELCはメッケル軟骨細胞のALPase活性を促進し,その後の石灰化の誘導因子として作用する可能性が示唆された。The effects of elcatonin (ELC) on Meckel\u27s cartilage obtained from 17-day embryonic mice were investigated using cell and organ cultures. Specimens for cell and organ cultures were cultured for 4 weeks in different media as follows: Control medium, alpha-modified Eagle\u27s medium (α-MEM); β-Gly medium, α-MEM plus β-glycerophosphate (β-Gly); ELC medium,α-MEM plus ELC; and β-Gly & ELC medium,α-MEM plus β-Gly plus ELC. Specimens were analyzed by histological and histochemical methods, including immunohistochemistry for alkaline phosphatase (ALPase) activity and bromodeoxyuridine (BrdU) incorporation. Von Kossa staining revealed that the ELC medium inducedeffective calcification similar to β-Gly medium, while BrdU incorporation showed that there was no significant difference in the rates of cell proliferation between Control medium and ELC medium. Histochemical and immunofluorescence staining indicated that ALPase was activated prior to matrix calcification in cell and organ cultures. β-Gly & ELC medium induced synergistically the highest level of matrix calcification and ALPase activity. The present results suggest the possibility that ELC accelerates activity of ALPase in Meckel\u27s chondrocytes and subsequently induces matrix calcification

MicroRNAs and Osteolytic Bone Metastasis: The Roles of MicroRNAs in Tumor-Induced Osteoclast Differentiation

Osteolytic bone metastasis frequently occurs in the later stages of breast, lung, and several other cancers. Osteoclasts, the only cells that resorb bone, are hijacked by tumor cells, which break down bone remodeling systems. As a result, osteolysis occurs and may cause patients to suffer bone fractures, pain, and hypercalcemia. It is important to understand the mechanism of bone metastasis to establish new cancer therapies. MicroRNAs are small, noncoding RNAs that are involved in various biological processes, including cellular differentiation, proliferation, apoptosis, and tumorigenesis. MicroRNAs have significant clinical potential, including their use as new therapeutic targets and disease-specific biomarkers. Recent studies have revealed that microRNAs are involved in osteoclast differentiation and osteolytic bone metastasis. In this review focusing on microRNAs, the author discusses the roles of microRNAs in osteoclastogenesis and osteolytic bone metastasis

MicroRNAs: Potential Biomarkers and Therapeutic Targets for Alveolar Bone Loss in Periodontal Disease

Periodontal disease is an inflammatory disease caused by bacterial infection of tooth-supporting structures, which results in the destruction of alveolar bone. Osteoclasts play a central role in bone destruction. Osteoclasts are tartrate-resistant acid phosphatase (TRAP)-positive multinucleated giant cells derived from hematopoietic stem cells. Recently, we and other researchers revealed that microRNAs are involved in osteoclast differentiation. MicroRNAs are novel, single-stranded, non-coding, small (20–22 nucleotides) RNAs that act in a sequence-specific manner to regulate gene expression at the post-transcriptional level through cleavage or translational repression of their target mRNAs. They regulate various biological activities such as cellular differentiation, apoptosis, cancer development, and inflammatory responses. In this review, the roles of microRNAs in osteoclast differentiation and function during alveolar bone destruction in periodontal disease are described