Intermittent hypoxia inhibits mandibular cartilage growth with reduced TGF-β and SOX9 expressions in neonatal rats.
Intermittent hypoxia inhibits mandibular cartilage growth with reduced TGF-β and SOX9 expressions in neonatal rats.
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间歇性低氧抑制新生大鼠下颌骨软骨生长并降低转化生长因子-β和胰岛素样生长因子9的表达。
DOI：
10.1038/s41598-020-80303-3
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发表时间：
2021-01-13
影响因子：
4.6
通讯作者：
Ono T
中科院分区：
文献类型：
--
作者：
Lekvijittada K;Hosomichi J;Maeda H;Hong H;Changsiripun C;Kuma YI;Oishi S;Suzuki JI;Yoshida KI;Ono T
间歇性缺氧（IH）与骨骼生长有关。然而，IH对软骨生长和代谢的影响尚不清楚。我们比较了IH对1周龄雄性Sprague-Dawley大鼠下颌髁突纤维软骨和胫骨透明软骨中软骨细胞增殖和成熟的影响。将大鼠暴露于常氧空气（n = 9）或IH（20个循环/h，最低点，4%O2;峰值，21%O2; 0%CO2）（n = 9），每天8 h。IH阻碍体重增加，但不延长胫骨。IH还增加了下颌骨髁状突头的松质骨矿物质和体积骨矿物质密度。髁突变薄，胫骨软骨无明显变薄。IH减少成熟和增加肥大的软骨细胞层的中，后下颌骨软骨。PCR结果显示，IH通过下调TGF-β和SOX 9的表达，上调X型胶原的表达，使髁突纤维软骨的增殖和成熟向肥大分化和骨化方向发展。胫骨生长板透明软骨中不存在这些效应。我们的研究结果表明，暴露于IH的新生大鼠显示不发达的下颌升支/髁突，而抑制软骨发生标记物的表达检测到生长受限的髁突软骨。
Intermittent hypoxia (IH) has been associated with skeletal growth. However, the influence of IH on cartilage growth and metabolism is unknown. We compared the effects of IH on chondrocyte proliferation and maturation in the mandibular condyle fibrocartilage and tibial hyaline cartilage of 1-week-old male Sprague–Dawley rats. The rats were exposed to normoxic air (n = 9) or IH at 20 cycles/h (nadir, 4% O2; peak, 21% O2; 0% CO2) (n = 9) for 8 h each day. IH impeded body weight gain, but not tibial elongation. IH also increased cancellous bone mineral and volumetric bone mineral densities in the mandibular condylar head. The mandibular condylar became thinner, but the tibial cartilage did not. IH reduced maturative and increased hypertrophic chondrocytic layers of the middle and posterior mandibular cartilage. PCR showed that IH shifted proliferation and maturation in mandibular condyle fibrocartilage toward hypertrophic differentiation and ossification by downregulating TGF-β and SOX9, and upregulating collagen X. These effects were absent in the tibial growth plate hyaline cartilage. Our results showed that neonatal rats exposed to IH displayed underdeveloped mandibular ramus/condyles, while suppression of chondrogenesis marker expression was detected in the growth-restricted condylar cartilage.
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