Roles of Ihh signaling in chondroprogenitor function in postnatal condylar cartilage.
Roles of Ihh signaling in chondroprogenitor function in postnatal condylar cartilage.
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DOI：
10.1016/j.matbio.2018.02.011
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发表时间：
2018-04
期刊：
影响因子：
--
通讯作者：
Koyama E
中科院分区：
文献类型：
--
作者：
Kurio N;Saunders C;Bechtold TE;Salhab I;Nah HD;Sinha S;Billings PC;Pacifici M;Koyama E
小鼠颞下颌关节髁突关节软骨由关节面附近的祖细胞发育而来，这些祖细胞增殖、经历软骨形成并成熟为肥大的软骨细胞。然而，目前尚不清楚这些过程是如何调节的，特别是出生后。在这里，我们专注于顶端多态层丰富的祖细胞，并询问是否表型和命运的细胞需要信号的印度刺猬（Ihh）以前研究在发展长骨。在新生小鼠的髁突中，顶端多态/祖细胞层约为10个细胞层厚，并表达关节基质标志物腱生蛋白-C（Tn-C），下面的厚细胞层表达Tn-C以及软骨形成主调节因子Sox 9。到1个月时，髁突软骨已获得其完整宽度，但沿其主纵轴沿着变薄，并显示肥大的软骨细胞。到3个月时，关节软骨由2-3个细胞层厚的表面细胞和表达Tn-C和Sox 9的软骨祖细胞区以及显示垂直基质隔的软骨细胞底部区组成。在幼年小鼠中的EdU细胞示踪显示，软骨祖细胞转化为软骨细胞和肥大软骨细胞分别需要约48和72小时。值得注意的是，在3个月大的小鼠中注射EdU在96小时前标记了祖细胞和成熟的软骨细胞。幼年/早期成年小鼠中Ihh的条件性消融损害了软骨祖细胞的组织和功能，并导致软骨祖细胞和软骨细胞增殖减少。突变髁突的表型随着时间的推移而恶化，如凋亡软骨细胞发生率，异位软骨细胞肥大，软骨细胞列紊乱和软骨下骨退化。在髁突顶端细胞的微团培养物中，刺猬（Hh）处理刺激软骨形成和碱性磷酸酶（AP酶）活性，而HhAntag处理抑制两者。我们的研究结果表明，软骨祖细胞层是不断参与髁状突生长出生后，其组织和功能依赖于刺猬信号。
Condylar articular cartilage in mouse temporomandibular joint develops from progenitor cells near the articulating surface that proliferate, undergo chondrogenesis and mature into hypertrophic chondrocytes. However, it remains unclear how these processes are regulated, particularly postnatally. Here we focused on the apical polymorphic layer rich in progenitors and asked whether the phenotype and fate of the cells require signaling by Indian hedgehog (Ihh) previously studied in developing long bones. In condyles in newborn mice, the apical polymorphic/progenitor cell layer was ~10 cell layer-thick and expressed the articular matrix marker Tenascin-C (Tn-C), and the underlying thick cell layer expressed Tn-C as well as the chondrogenic master regulator Sox9. By 1 month, condylar cartilage had gained its full width, but became thinner along its main longitudinal axis and displayed hypertrophic chondrocytes. By 3 months, articular cartilage consisted of a 2–3 cell layer-thick zone of superficial cells and chondroprogenitors expressing both Tn-C and Sox9 and a bottom zone of chondrocytes displaying vertical matrix septa. EdU cell tracing in juvenile mice revealed that conversion of chondroprogenitors into chondrocytes and hypertrophic chondrocytes required about 48 and 72 hrs, respectively. Notably, EdU injection in 3 month-old mice labeled both progenitors and maturing chondrocytes by 96 hrs. Conditional ablation of Ihh in juvenile/early adult mice compromised chondroprogenitor organization and function and led to reduced chondroprogenitor and chondrocyte proliferation. The phenotype of mutant condyles worsened over time as indicated by apoptotic chondrocyte incidence, ectopic chondrocyte hypertrophy, chondrocyte column derangement and subchondral bone deterioration. In micromass cultures of condylar apical cells, hedgehog (Hh) treatment stimulated chondrogenesis and alkaline phosphatase (APase) activity, while treatment with HhAntag inhibited both. Our findings indicate that the chondroprogenitor layer is continuously engaged in condylar growth postnatally and its organization and functioning depend on hedgehog signaling.
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影响因子：
7.6
作者：
Kinumatsu, T.;Shibukawa, Y.;Koyama, E.
通讯作者：
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2.9
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作者：
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25
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