LIGHT/TNFSF14 increases osteoclastogenesis and decreases osteoblastogenesis in multiple myeloma-bone disease.
LIGHT/TNFSF14 increases osteoclastogenesis and decreases osteoblastogenesis in multiple myeloma-bone disease.
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DOI：
10.18632/oncotarget.2633
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发表时间：
2014-12-30
期刊：
影响因子：
--
通讯作者：
Grano M
中科院分区：
文献类型：
--
作者：
Brunetti G;Rizzi R;Oranger A;Gigante I;Mori G;Taurino G;Mongelli T;Colaianni G;Di Benedetto A;Tamma R;Ingravallo G;Napoli A;Faienza MF;Mestice A;Curci P;Specchia G;Colucci S;Grano M
莱特是一名肿瘤坏死因子超家族成员，参与T细胞稳态和与类风湿性关节炎相关的侵蚀性骨病。在此，我们调查了LIGH是否在多发性骨髓瘤(MM)骨病中起作用。我们发现MM骨病患者外周血和骨髓(BM)中CD14+单核细胞、CD8+T细胞和中性粒细胞过度产生LIGH。我们还发现光诱导了破骨细胞的形成，抑制了成骨细胞的形成。在健康供者的培养中，光以RANKL依赖和非独立的方式诱导破骨细胞的形成。在次适浓度的RANKL存在下，LIGH和RANKL通过AKT、NFκB和JNK信号通路的磷酸化，协同刺激破骨细胞的形成。在骨病患者的骨髓标本培养中，LIGH抑制CFU-F和CFU-OB的形成以及成骨标志物包括I型胶原、骨钙素和骨涎蛋白-II的表达。光间接抑制成骨细胞的形成，部分是通过单核细胞表达的硬化素。总之，我们的发现首次为光在多发性骨髓瘤骨病发展中的作用提供了证据。
LIGHT, a TNF superfamily member, is involved in T-cell homeostasis and erosive bone disease associated with rheumatoid arthritis. Herein, we investigated whether LIGHT has a role in Multiple Myeloma (MM)-bone disease. We found that LIGHT was overproduced by CD14+ monocytes, CD8+ T-cells and neutrophils of peripheral blood and bone marrow (BM) from MM-bone disease patients. We also found that LIGHT induced osteoclastogenesis and inhibited osteoblastogenesis. In cultures from healthy-donors, LIGHT induced osteoclastogenesis in RANKL-dependent and -independent manners. In the presence of a sub-optimal RANKL concentration, LIGHT and RANKL synergically stimulated osteoclast formation, through the phosphorylation of Akt, NFκB and JNK pathways. In cultures of BM samples from patients with bone disease, LIGHT inhibited the formation of CFU-F and CFU-OB as well as the expression of osteoblastic markers including collagen-I, osteocalcin and bone sialoprotein-II. LIGHT indirectly inhibited osteoblastogenesis in part through sclerostin expressed by monocytes. In conclusion, our findings for the first time provide evidence for a role of LIGHT in MM-bone disease development.
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影响因子：
11.2
作者：
Giuliani, Nicola;Lisignoli, Gina;Rizzoli, Vittorio
通讯作者：
Rizzoli, Vittorio
影响因子：
4.8
作者：
Harrop, JA;McDonnell, PC;Young, PR
通讯作者：
Young, PR
影响因子：
4.8
作者：
Bellido, T;Borba, VZC;Manolagas, SC
通讯作者：
Manolagas, SC
影响因子：
6.2
作者：
Alexander, Kylie A.;Chang, Ming K.;Pettit, Allison R.
通讯作者：
Pettit, Allison R.
DOI：
10.1111/j.1749-6632.2011.06196.x
发表时间：
2011-01-01
期刊：
SKELETAL BIOLOGY AND MEDICINE I
影响因子：
--
作者：
Brunetti, Giacomina;Oranger, Angela;Colucci, Silvia
通讯作者：
Colucci, Silvia