Deletion of IL-17ra in osteoclast precursors increases bone mass by decreasing osteoclast precursor abundance.
Deletion of IL-17ra in osteoclast precursors increases bone mass by decreasing osteoclast precursor abundance.
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代谢性骨病，如骨质疏松症，通常反映了骨吸收破骨细胞数量和活动的增加，从而导致骨量的损失。炎症介质已被确定为破骨细胞形成和活动的驱动因素。炎性细胞因子IL-17家族作为骨形成和骨吸收的重要贡献者而受到关注。大多数IL-17细胞因子通过含有IL-17a受体（IL-17ra）的受体复合物传递信号；然而，IL-17ra信号在破骨细胞中的作用仍然难以捉摸。在这项研究中，我们使用LysM-Cre有条件地删除破骨细胞前体中的IL-17ra，并评估了骨骼成熟的雄性和雌性条件敲除小鼠和对照小鼠的表型。条件基因敲除小鼠在阑尾和中轴骨骼中显示出骨小梁微结构的增加。体外对破骨细胞形成的评估显示，IL-17ra的缺失减少了破骨细胞的数量，这在体内通过组织形态计量学得到了证实。这种表型可能是由IL-17ra条件敲除小鼠中较低丰度的破骨细胞前体驱动的。这项研究表明，IL-17ra信号在破骨细胞前可以促进破骨细胞的形成和随后的骨质流失。
Metabolic bone diseases, such as osteoporosis, typically reflect an increase in the number and activity of bone-resorbing osteoclasts that result in a loss of bone mass. Inflammatory mediators have been identified as drivers of both osteoclast formation and activity. The IL-17 family of inflammatory cytokines has gained attention as important contributors to both bone formation and resorption. The majority of IL-17 cytokines signal through receptor complexes containing IL-17a receptor (IL-17ra); however, the role of IL-17ra signaling in osteoclasts remains elusive. In this study, we conditionally deleted IL-17ra in osteoclast precursors using LysM-Cre and evaluated the phenotypes of skeletally mature male and female conditional knockout and control mice. The conditional knockout mice displayed an increase in trabecular bone microarchitecture in both the appendicular and axial skeleton. Assessment of osteoclast formation in vitro revealed that deletion of IL-17ra decreased osteoclast number, which was confirmed in vivo using histomorphometry. This phenotype was likely driven by a lower abundance of osteoclast precursors in IL-17ra conditional knockout mice. This study suggests that IL-17ra signaling in preosteoclasts can contribute to osteoclast formation and subsequent bone loss.
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影响因子：
4
作者：
DeSelm, Carl J.;Takahata, Yoshifumi;Warren, Julia;Chappel, Jean C.;Khan, Taimur;Li, Xiaoxia;Liu, Caini;Choi, Yongwon;Kim, Youngmi Faith;Zou, Wei;Teitelbaum, Steven L.
通讯作者：
Teitelbaum, Steven L.
白细胞介素 17 受体 A 调节体内单核细胞亚群和巨噬细胞的生成。
影响因子：
3.7
作者：
Ge S;Hertel B;Susnik N;Rong S;Dittrich AM;Schmitt R;Haller H;von Vietinghoff S
通讯作者：
von Vietinghoff S
影响因子：
4.9
作者：
Adamopoulos IE;Chao CC;Geissler R;Laface D;Blumenschein W;Iwakura Y;McClanahan T;Bowman EP
通讯作者：
Bowman EP
影响因子：
5.2
作者：
Roberts, Joseph L.;Liu, Guanglu;Drissi, Hicham
通讯作者：
Drissi, Hicham
影响因子：
3.9
作者：
Kitami, Satoshi;Tanaka, Hideki;Maeno, Masao
通讯作者：
Maeno, Masao