Department of Molecular Pathology, Ehime University Graduate School of Medicine, Shitsukawa, Toon City 791-0295, Japan.
Department of Diagnostic Pathology, Ehime University Hospital, Shitsukawa, Toon City 791-0295, Japan.
Int J Mol Sci. 2019 Nov 20;20(23):5840. doi: 10.3390/ijms20235840.
The longitudinal growth of long bone, regulated by an epiphyseal cartilaginous component known as the "growth plate", is generated by epiphyseal chondrocytes. The growth plate provides a continuous supply of chondrocytes for endochondral ossification, a sequential bone replacement of cartilaginous tissue, and any failure in this process causes a wide range of skeletal disorders. Therefore, the cellular and molecular characteristics of the growth plate are of interest to many researchers. Hedgehog (Hh), well known as a mitogen and morphogen during development, is one of the best known regulatory signals in the developmental regulation of the growth plate. Numerous animal studies have revealed that signaling through the Hh pathway plays multiple roles in regulating the proliferation, differentiation, and maintenance of growth plate chondrocytes throughout the skeletal growth period. Furthermore, over the past few years, a growing body of evidence has emerged demonstrating that a limited number of growth plate chondrocytes transdifferentiate directly into the full osteogenic and multiple mesenchymal lineages during postnatal bone development and reside in the bone marrow until late adulthood. Current studies with the genetic fate mapping approach have shown that the commitment of growth plate chondrocytes into the skeletal lineage occurs under the influence of epiphyseal chondrocyte-derived Hh signals during endochondral bone formation. Here, we discuss the valuable observations on the role of the Hh signaling pathway in the growth plate based on mouse genetic studies, with some emphasis on recent advances.
长骨的纵向生长由称为“生长板”的骺软骨成分调节，由骺软骨细胞产生。生长板为软骨内成骨提供源源不断的软骨细胞，这是一个连续的软骨组织被骨替代的过程，而这个过程中的任何失败都会导致广泛的骨骼疾病。因此，生长板的细胞和分子特征引起了许多研究人员的兴趣。Hedgehog（Hh）在发育过程中是一种有丝分裂原和形态发生素，是生长板发育调控中最著名的调节信号之一。大量动物研究表明，Hh 通路的信号转导在调节生长板软骨细胞的增殖、分化和维持方面发挥着多种作用，贯穿整个骨骼生长周期。此外，在过去的几年中，越来越多的证据表明，在出生后骨发育过程中，有限数量的生长板软骨细胞直接转分化为完全成骨和多种间充质谱系，并存在于骨髓中，直到成年后期。目前，通过遗传命运图谱的研究表明，在骺软骨内成骨过程中，生长板软骨细胞向骨骼谱系的定向分化受到骺软骨细胞衍生的 Hh 信号的影响。在这里，我们根据小鼠遗传研究讨论了 Hh 信号通路在生长板中的作用的有价值的观察结果，并强调了一些最新进展。
