Mehrara B J, Most D, Chang J, Bresnick S, Turk A, Schendel S A, Gittes G K, Longaker M T
Institute of Reconstructive Plastic Surgery, and the Department of Surgery, New York University Medical Center, NY 10016, USA.
Plast Reconstr Surg. 1999 Aug;104(2):435-44. doi: 10.1097/00006534-199908000-00017.
Numerous studies have found dura mater-calvarial mesenchyme interactions during calvarial bone induction; however, the exact molecular mechanisms governing these inductive events remain unknown. Recent studies have implicated basic fibroblast growth factor (FGF-2) and transforming growth factor-beta1 (TGF-beta1) in regulating bone formation. The purpose of this study was, therefore, to investigate the expression of FGF-2 and TGF-beta1 during calvarial bone formation in rats. Eight rats were killed on embryonic days 14, 18, and 20 and neonatal day 1 (n = 32). Four animals at each time point were analyzed by in situ hybridization, and the remainder were analyzed by immunohistochemistry. The results indicated that the dura mater underlying the developing calvarial bone strongly expressed FGF-2 and TGF-beta1 mRNA at all time points examined. In contrast, minimal growth factor expression was noted in the overlying calvarial mesenchyme until embryonic day 18, but it increased significantly with increasing age. Importantly, FGF-2 and TGF-beta1 mRNA expression in the dura mater underlying the developing calvarium preceded and was significantly greater than expression in the calvarium mesenchyme (p < 0.05). Interestingly, minimal expression of FGF-2 and TGF-beta1 mRNA was noted for all time points in the dura mater underlying the posterior frontal suture and within the posterior frontal suture connective tissue (p < 0.01 when compared with the dura mater underlying the developing calvarium). Immunohistochemical findings closely paralleled mRNA expression, with intense staining for FGF-2 and TGF-beta1 in the dura mater underlying the developing calvarial mesenchyme. Increasing FGF-2 and TGF-beta1 staining was noted within calvarial osteoblasts with increasing age, particularly in cells located near the endocranial surface (i.e., in contact with the developing dura mater). These findings, together with the known biologic functions of FGF-2 and TGF-beta1, implicate these growth factors in the regulation of calvarial bone growth by the developing dura mater. The possible mechanisms of this interaction are discussed.
众多研究已发现颅骨诱导过程中硬脑膜与颅骨间充质的相互作用；然而，调控这些诱导事件的确切分子机制仍不清楚。近期研究表明碱性成纤维细胞生长因子（FGF - 2）和转化生长因子 - β1（TGF - β1）参与调节骨形成。因此，本研究的目的是调查大鼠颅骨形成过程中FGF - 2和TGF - β1的表达情况。在胚胎第14、18和20天以及新生第1天处死8只大鼠（n = 32）。每个时间点的4只动物通过原位杂交进行分析，其余动物通过免疫组织化学进行分析。结果表明，在所有检测时间点，发育中颅骨下方的硬脑膜均强烈表达FGF - 2和TGF - β1 mRNA。相比之下，直到胚胎第18天，覆盖的颅骨间充质中生长因子表达极少，但随着年龄增长显著增加。重要的是，发育中颅骨下方硬脑膜中FGF - 2和TGF - β1 mRNA表达先于颅骨间充质且显著高于其表达水平（p < 0.05）。有趣的是，在额后缝下方的硬脑膜以及额后缝结缔组织内，所有时间点FGF - 2和TGF - β1 mRNA表达均极少（与发育中颅骨下方硬脑膜相比，p < 0.01）。免疫组织化学结果与mRNA表达密切平行，发育中颅骨间充质下方硬脑膜中FGF - 2和TGF - β1染色强烈。随着年龄增长，颅骨成骨细胞内FGF - 2和TGF - β1染色增加，尤其是位于颅内膜表面附近（即与发育中的硬脑膜接触）的细胞。这些发现，连同FGF - 2和TGF - β1已知的生物学功能，表明这些生长因子参与发育中的硬脑膜对颅骨生长的调节。本文讨论了这种相互作用的可能机制。
