摘要：
Bone metastases occur in patients with advanced-stage prostate cancer(PCa). The cell-cell interaction between PCa and the bone microenvironment forms a vicious cycle that modulates the bone microenvironment, increases bone deformities, and drives tumor growth in the bone. However, the molecular mechanisms of PCa-mediated modulation of the bone microenvironment are complex and remain poorly defined. Here, we evaluated growth differentiation factor-15(GDF15) function using in vivo preclinical PCa-bone metastasis mouse models and an in vitro bone cell coculture system. Our results suggest that PCa-secreted GDF15 promotes bone metastases and induces bone microarchitectural alterations in a preclinical xenograft model. Mechanistic studies revealed that GDF15 increases osteoblast function and facilitates the growth of PCa in bone by activating osteoclastogenesis through osteoblastic production of CCL2 and RANKL and recruitment of osteomacs. Altogether, our findings demonstrate the critical role of GDF15 in the modulation of the bone microenvironment and subsequent development of PCa bone metastasis.
摘要：
Objective:To demonstrate the effect of dieckol from Eisenia bicyclis on osteoclastogenesis using RAW 264.7 cells.Methods:Murine macrophage RAW 264.7 cells were subjected to dieckol treatment,followed by treatment with receptor activator of nuclear factor kappa-B ligand(RANKL)to induce osteoclastogenesis.Tartrate-resistant acid phosphatase(TRAP)activity was examined using a TRAP activity kit.Western blotting analysis was conducted to examine the level of osteoclast-related factors,including TRAP and calcitonin receptor(CTR),transcriptional factors,including c-Fos,c-Jun,and nuclear factor of activated T cells cytoplasmic 1(NFATc1),nuclear factor kappa-B(NF-κB),extracellular signal-regulated kinase(ERK),and c-Jun N-terminal kinase(JNK).Immunofluorescence staining was conducted to examine the expression of c-Fos,c-Jun,and NFATc1.Results:Among the four phlorotannin compounds present in Eisenia bicyclis,dieckol significantly hindered osteoclast differentiation and expression of RANKL-induced TRAP and CTR.In addition,dieckol downregulated the expression levels of c-Fos,c-Jun,NFATc1,ERK,and JNK,and suppressed NF-κB signaling.Conclusions:Dieckol can suppress RANKL-induced osteoclastogenesis.Therefore,it has therapeutic potential in treating osteoclastogenesis-associated diseases.
摘要：
骨巨細(xì)胞瘤(giant cell tumor of bone,GCTB)是一種好發(fā)于長(zhǎng)骨干骺端的局部侵襲性生長(zhǎng)的原發(fā)性骨腫瘤,是交界性腫瘤,極少發(fā)生轉(zhuǎn)移,但有惡變可能,常會(huì)導(dǎo)致嚴(yán)重骨質(zhì)破壞,治療難點(diǎn)是手術(shù)后極易復(fù)發(fā)。細(xì)胞核因子κB受體活化因子配體(receptor activator of NF-κB ligand,RANKL)是蝕骨細(xì)胞初成、發(fā)揮功能所必需的跨膜及可溶性蛋白。RANKL過表達(dá)引發(fā)骨質(zhì)溶解破壞,導(dǎo)致GCTB瘤體逐步膨脹性、局部侵襲性生長(zhǎng)。
摘要：
本發(fā)明提供了一種特異性結(jié)合RANKL靶向治療藥物的抗體，所述抗體由2條相同的重鏈和2條相同的輕鏈組成，其中所述重鏈的可變區(qū)具有三個(gè)抗原決定簇區(qū)域，所述重鏈的可變區(qū)的抗原決定簇區(qū)域的氨基酸序列選自如SEQ ID NO.7?SEQ ID NO.15所示的氨基酸序列；所述輕鏈的可變區(qū)具有三個(gè)抗原決定簇區(qū)域，所述輕鏈的可變區(qū)的抗原決定簇區(qū)域的氨基酸序列選自如SEQ ID NO.16?SEQ ID NO.24所示的氨基酸序列。本發(fā)明的抗體能夠與地舒單抗特異性結(jié)合，并且各抗體之間不存在競(jìng)爭(zhēng)關(guān)系，從而有效、準(zhǔn)確地檢測(cè)血清中地舒單抗的濃度。
摘要：
本發(fā)明提供了一種特異性結(jié)合RANKL靶向治療藥物的抗體，所述抗體由2條相同的重鏈和2條相同的輕鏈組成，其中重鏈的可變區(qū)具有三個(gè)抗原決定簇區(qū)域，所述重鏈的可變區(qū)的三個(gè)抗原決定簇區(qū)域的氨基酸序列如SEQ ID NO.3、4、5所示；所述輕鏈的可變區(qū)具有三個(gè)抗原決定簇區(qū)域，所述輕鏈的可變區(qū)的三個(gè)抗原決定簇區(qū)域的氨基酸序列自如SEQ IDNO.6、7、8所示。本發(fā)明的抗體能夠與地舒單抗特異性結(jié)合，從而有效、準(zhǔn)確地定性、定量檢測(cè)血清中的地舒單抗。
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