Bif-1/Endophilin B1/SH3GLB1 regulates bone homeostasis
Bif-1/Endophilin B1/SH3GLB1 regulates bone homeostasis
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DOI：
10.1002/jcb.29193
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发表时间：
2019-11-01
影响因子：
4
通讯作者：
Jimi, Eijiro
中科院分区：
文献类型：
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作者：
Touyama, Kenya;Khan, Masud;Jimi, Eijiro
骨骼组织的动态平衡是通过破骨细胞性骨吸收和成骨细胞性骨形成的平衡来维持的。自噬和凋亡对于维持细胞和组织的内稳态和正常发育是必不可少的。我们发现Bax相互作用因子1(Bif-1/Endophlin B1/SH3GLB1)在破骨细胞形成过程中上调，参与自噬和细胞凋亡。此外，成熟的破骨细胞在胞浆中表达Bif-1，特别是在核周和足体，提示Bif-1调节破骨细胞性骨吸收。BIF-1基因缺陷(Bif-1(-/-))小鼠的骨小梁体积和骨小梁数量增加。组织学分析表明，Bif-1(-/-)小鼠的破骨细胞数量增加。与体内结果一致的是，核因子-kappa B受体激活剂配体(RANKL)在Bif-1(-/-)小鼠体内诱导的破骨细胞形成加快，但不影响RANKL诱导的RANKL诱导的RANK下游信号的激活，如核因子-kappa B和丝裂原激活蛋白激酶(MAPKs)、破骨细胞前体CD115/RANK的表达、破骨细胞骨吸收活性和存活率。出乎意料的是，Bif-1(-/-)小鼠的骨形成率和成骨细胞表面都大幅增加。用β-甘油磷酸(β-GP)和抗坏血酸(A.A)治疗可促进Bif-1(-/-)小鼠的成骨细胞分化和矿化。Bif-1(-/-)小鼠骨髓细胞在加或不加β-gp和A.A处理后的集落形成率明显高于野生型(WT)小鼠，提示Bif-1(-/-)小鼠的细胞具有比WT小鼠更高的克隆形成和自我更新能力。综上所述，Bif-1可能通过控制破骨细胞和成骨细胞的分化和功能来调节骨骼的动态平衡(235字)。
Skeletal tissue homeostasis is maintained via the balance of osteoclastic bone resorption and osteoblastic bone formation. Autophagy and apoptosis are essential for the maintenance of homeostasis and normal development in cells and tissues. We found that Bax-interacting factor 1 (Bif-1/Endophillin B1/SH3GLB1), involving in autophagy and apoptosis, was upregulated during osteoclastogenesis. Furthermore, mature osteoclasts expressed Bif-1 in the cytosol, particularly the perinuclear regions and podosome, suggesting that Bif-1 regulates osteoclastic bone resorption. Bif-1-deficient (Bif-1(-/-)) mice showed increased trabecular bone volume and trabecular number. Histological analyses indicated that the osteoclast numbers increased in Bif-1(-/-) mice. Consistent with the in vivo results, osteoclastogenesis induced by receptor activator of nuclear factor-kappa B (NF-kappa B) ligand (RANKL) was accelerated in Bif-1(-/-) mice without affecting RANKL-induced activation of RANK downstream signals, such as NF-kappa B and mitogen-activated protein kinases (MAPKs), CD115/RANK expression in osteoclast precursors, osteoclastic bone-resorbing activity and the survival rate. Unexpectedly, both the bone formation rate and osteoblast surface substantially increased in Bif-1(-/-) mice. Treatment with beta-glycerophosphate (beta-GP) and ascorbic acid (A.A) enhanced osteoblastic differentiation and mineralization in Bif-1(-/-) mice. Finally, bone marrow cells from Bif-1(-/-) mice showed a significantly higher colony-forming efficacy by the treatment with or without beta-GP and A.A than cells from wild-type (WT) mice, suggesting that cells from Bif-1(-/-) mice had higher clonogenicity and self-renewal activity than those from WT mice. In summary, Bif-1 might regulate bone homeostasis by controlling the differentiation and function of both osteoclasts and osteoblasts (235 words).