Mitochondrial fatty acid β-oxidation is important for normal osteoclast formation in growing female mice.
Mitochondrial fatty acid β-oxidation is important for normal osteoclast formation in growing female mice.
复制标题
线粒体脂肪酸β-氧化对生长中雌性小鼠的正常破骨细胞形成很重要。
DOI：
10.3389/fphys.2022.997358
复制
发表时间：
2022
影响因子：
4
通讯作者：
Riddle, Ryan C.
中科院分区：
文献类型：
--
作者：
Kushwaha, Priyanka;Alekos, Nathalie S.;Kim, Soohyun P.;Li, Zhu;Wolfgang, Michael J.;Riddle, Ryan C.
骨骼重塑是一个需要能量的过程，与营养供应和代谢激素水平有关。虽然最近的研究已经检查了成骨细胞骨形成的代谢需求，但对破骨细胞骨吸收的能量需求知之甚少。成熟破骨细胞中线粒体的丰富表明，产生有利于羟基磷灰石电离、基质降解酶分泌和再吸收过程中运动的酸化微环境需要显著的能量能力。为了研究线粒体长链脂肪酸β-氧化对破骨细胞发育的贡献，我们破坏了骨髓系细胞中肉毒碱棕榈酰转移酶-2（Cpt 2）的表达。在RANKL和M-CSF刺激的骨髓培养物中，脂肪酸氧化显著增加，microCT分析显示，破骨细胞中长链脂肪酸氧化的遗传抑制显著增加了雌性小鼠的骨小梁体积，继发于破骨细胞数量减少。与这些数据一致，从Cpt 2突变体中分离的破骨细胞前体表现出形成大的多核破骨细胞的能力降低，这不是由外源性葡萄糖或丙酮酸拯救的，并且表现出充满活力的应激反应的迹象。总之，我们的数据表明，线粒体长链脂肪酸氧化的破骨细胞是所需的正常骨吸收，因为它的抑制产生的内在缺陷，破骨细胞形成。
Skeletal remodeling is an energy demanding process that is linked to nutrient availability and the levels of metabolic hormones. While recent studies have examined the metabolic requirements of bone formation by osteoblasts, much less is known about the energetic requirements of bone resorption by osteoclasts. The abundance of mitochondria in mature osteoclasts suggests that the production of an acidified micro-environment conducive to the ionization of hydroxyapatite, secretion of matrix-degrading enzymes, and motility during resorption requires significant energetic capacity. To investigate the contribution of mitochondrial long chain fatty acid β-oxidation to osteoclast development, we disrupted the expression of carnitine palmitoyltransferase-2 (Cpt2) in myeloid-lineage cells. Fatty acid oxidation increases dramatically in bone marrow cultures stimulated with RANKL and M-CSF and microCT analysis revealed that the genetic inhibition of long chain fatty acid oxidation in osteoclasts significantly increases trabecular bone volume in female mice secondary to reduced osteoclast numbers. In line with these data, osteoclast precursors isolated from Cpt2 mutants exhibit reduced capacity to form large-multinucleated osteoclasts, which was not rescued by exogenous glucose or pyruvate, and signs of an energetic stress response. Together, our data demonstrate that mitochondrial long chain fatty acid oxidation by the osteoclast is required for normal bone resorption as its inhibition produces an intrinsic defect in osteoclast formation.
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DOI：
10.1111/dom.12248
发表时间：
2014-08
期刊：
Diabetes, obesity & metabolism
影响因子：
--
作者：
Haynie KR;Vandanmagsar B;Wicks SE;Zhang J;Mynatt RL
通讯作者：
Mynatt RL
影响因子：
56.9
作者：
DAWSON, DM;KAPLAN, NO;GOODFRIEND, TL
通讯作者：
GOODFRIEND, TL
影响因子：
4.6
作者：
Dawodu, Damilola;Patecki, Margret;Kiyan, Yulia
通讯作者：
Kiyan, Yulia
影响因子：
3.3
作者：
KENDRICK, ZV;ELLIS, GS
通讯作者：
ELLIS, GS
影响因子：
8
作者：
Kim, Soohyun P.;Li, Zhu;Riddle, Ryan C.
通讯作者：
Riddle, Ryan C.