The Fungal Metabolite (+)-Terrein Abrogates Ovariectomy-Induced Bone Loss and Receptor Activator of Nuclear Factor-κB Ligand-Induced Osteoclastogenesis by Suppressing Protein Kinase-C α/βII Phosphorylation.
The Fungal Metabolite (+)-Terrein Abrogates Ovariectomy-Induced Bone Loss and Receptor Activator of Nuclear Factor-κB Ligand-Induced Osteoclastogenesis by Suppressing Protein Kinase-C α/βII Phosphorylation.
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真菌代谢产物（+） - 畸胎素通过抑制蛋白激酶-Cα/βIII磷酸化来消除核因子-κB配体诱导的骨造成骨质质发生的骨损失和受体激活剂。
DOI：
10.3389/fphar.2021.674366
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发表时间：
2021
影响因子：
5.6
通讯作者：
Takashiba S
中科院分区：
文献类型：
--
作者：
Sakaida K;Omori K;Nakayama M;Mandai H;Nakagawa S;Sako H;Kamei C;Yamamoto S;Kobayashi H;Ishii S;Ono M;Ibaragi S;Yamashiro K;Yamamoto T;Suga S;Takashiba S
骨质疏松症是一种常见的疾病，其特征是骨量和微结构的全身性损害，导致脆性骨折。由于骨质疏松症引起的严重骨丢失引发病理性骨折，从而降低日常生活活动和生活质量。因此，预防骨质疏松症已成为一个亟待解决的重要问题。我们已经报道，真菌次级代谢产物（+）-terrein（TER），一种来源于土曲霉的天然化合物，通过抑制活化T细胞核因子1（NFATc 1）表达（破骨细胞生成的主要调节因子），显示出核因子-κB配体受体激活因子（RANKL）诱导的破骨细胞分化。TER已被证明具有广泛的生物学和药理学益处;然而，其对骨代谢的影响尚不清楚。在这项研究中，我们使用小鼠卵巢切除骨质疏松症模型（OVX小鼠）研究了TER对股骨骨代谢的影响，然后使用小鼠骨髓巨噬细胞（mBK）研究了TER对RANKL信号转导的影响。体内给药TER显著改善OVX小鼠的骨密度、骨量和骨小梁数量（p < 0.01）。此外，TER抑制OVX小鼠组织切片中的TRAP和组织蛋白酶-K表达（p < 0.01）。在一项体外研究中，TER抑制RANKL诱导的PKCα/βII磷酸化，其参与NFATc 1的表达（p < 0.05）。PKC抑制剂GF 109203 X也抑制了mBclone和TER中RANKL诱导的破骨细胞生成。此外，TER抑制破骨细胞生成相关基因的表达，如Ocstamp、Dcstamp、Calcr、Atp 6v 0 d2、Oscar和Itgb 3（p < 0.01）。这些结果为TER作为抗骨质疏松症的新型治疗化合物的潜在治疗应用提供了有希望的证据。
Osteoporosis is a common disease characterized by a systemic impairment of bone mass and microarchitecture that results in fragility fractures. Severe bone loss due to osteoporosis triggers pathological fractures and consequently decreases the daily life activity and quality of life. Therefore, prevention of osteoporosis has become an important issue to be addressed. We have reported that the fungal secondary metabolite (+)-terrein (TER), a natural compound derived from Aspergillus terreus, has shown receptor activator of nuclear factor-κB ligand (RANKL)–induced osteoclast differentiation by suppressing nuclear factor of activated T-cell 1 (NFATc1) expression, a master regulator of osteoclastogenesis. TER has been shown to possess extensive biological and pharmacological benefits; however, its effects on bone metabolism remain unclear. In this study, we investigated the effects of TER on the femoral bone metabolism using a mouse-ovariectomized osteoporosis model (OVX mice) and then on RANKL signal transduction using mouse bone marrow macrophages (mBMMs). In vivo administration of TER significantly improved bone density, bone mass, and trabecular number in OVX mice (p < 0.01). In addition, TER suppressed TRAP and cathepsin-K expression in the tissue sections of OVX mice (p < 0.01). In an in vitro study, TER suppressed RANKL-induced phosphorylation of PKCα/βII, which is involved in the expression of NFATc1 (p < 0.05). The PKC inhibitor, GF109203X, also inhibited RANKL-induced osteoclastogenesis in mBMMs as well as TER. In addition, TER suppressed the expression of osteoclastogenesis-related genes, such as Ocstamp, Dcstamp, Calcr, Atp6v0d2, Oscar, and Itgb3 (p < 0.01). These results provide promising evidence for the potential therapeutic application of TER as a novel treatment compound against osteoporosis.
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影响因子：
6.2
作者：
Burge, Russel;Dawson-Hughes, Bess;Tosteson, Anna
通讯作者：
Tosteson, Anna
DOI：
10.1155/2019/2705263
发表时间：
2019-01-01
影响因子：
--
作者：
Lin, Haixiong;Wang, Xiaotong;Chen, Yongjun
通讯作者：
Chen, Yongjun
DOI：
10.1159/000496039
发表时间：
2018-01-01
期刊：
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology
影响因子：
--
作者：
Chen, Xiao;Li, Xiaoqun;Su, Jiacan
通讯作者：
Su, Jiacan
影响因子：
3.3
作者：
Arakawa, Masayuki;Someno, Tetsuya;Ikeda, Daishiro
通讯作者：
Ikeda, Daishiro
影响因子：
4.1
作者：
Raistrick, H;Smith, G
通讯作者：
Smith, G