Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Boston, MA 02115, USA.
Endocrine Unit, Massachusetts General Hospital, Boston, MA 02114, USA.
Development. 2018 Aug 10;145(15):dev163519. doi: 10.1242/dev.163519.
The bone tendon attachment site known as the enthesis comprises a transitional zone between bone and tendon, and plays an important role in enabling movement at this site. X-linked hypophosphatemia (XLH) is characterized by impaired activation of vitamin D, elevated serum FGF23 levels and low serum phosphate levels, which impair bone mineralization. Paradoxically, an important complication of XLH is mineralization of the enthesis (enthesopathy). Studies were undertaken to identify the cellular and molecular pathways important for normal post-natal enthesis maturation and to examine their role during the development of enthesopathy in mice with XLH (Hyp). The Achilles tendon entheses of Hyp mice demonstrate an expansion of hypertrophic-appearing chondrogenic cells by P14. Post-natally, cells in wild-type and Hyp entheses similarly descend from scleraxis- and Sox9-expressing progenitors; however, Hyp entheses exhibit an expansion of Sox9-expressing cells, and enhanced BMP and IHH signaling. These results support a role for enhanced BMP and IHH signaling in the development of enthesopathy in XLH.
已知的骨腱附着部位称为腱骨结合处，它由骨和腱之间的过渡区组成，在该部位的运动中起着重要作用。X 连锁低磷血症（XLH）的特征是维生素 D 活性受损，血清 FGF23 水平升高和血清磷酸盐水平降低，从而损害骨矿化。矛盾的是，XLH 的一个重要并发症是腱骨结合处（腱骨病）的矿化。进行了研究以确定正常出生后腱骨结合处成熟的重要细胞和分子途径，并在 XLH（Hyp）小鼠腱骨病的发展过程中研究其作用。Hyp 小鼠的跟腱腱骨结合处显示出 P14 时出现肥大样软骨细胞的扩张。出生后，野生型和 Hyp 腱骨结合处的细胞同样从表达 Scleraxis 和 Sox9 的祖细胞中下降；然而，Hyp 腱骨结合处表现出 Sox9 表达细胞的扩张，并增强了 BMP 和 IHH 信号。这些结果支持在 XLH 腱骨病的发展中增强的 BMP 和 IHH 信号的作用。
