Department of Anatomy & Cell Biology, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, Ontario, N6A 5C1, Canada.
Dentistry, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, Ontario, N6A 5C1, Canada.
Sci Rep. 2019 Feb 25;9(1):2708. doi: 10.1038/s41598-018-35805-6.
During skin healing, periostin facilitates myofibroblast differentiation through a β1 integrin/FAK dependent mechanism and continued expression is associated with scarring. In contrast to skin, gingival tissue does not typically scar upon injury, but the role of periostin in gingival healing has never been investigated. Using a rat gingivectomy model, we show that the gingival architecture is re-established within 14 days of wounding. Periostin mRNA levels peak at day 7 post-wounding, with persistence of periostin protein in the connective tissue through day 14. Collagen type I and lysyl oxidase mRNA levels peak at day 7 post wounding, which corresponded with the peak of fibroblast proliferation. Although α-smooth muscle actin mRNA levels increased 200-fold in the tissue, no myofibroblasts were detected in the regenerating tissue. In vitro, human gingival fibroblast adhesion on periostin, but not collagen, was inhibited by blocking β1 integrins. Fibroblasts cultured on periostin exhibited similar rates of proliferation and myofibroblast differentiation to cells cultured on collagen only. However, human gingival fibroblasts cultured in the presence of periostin exhibited significantly increased fibronectin and collagen mRNA levels. Increases in fibronectin production were attenuated by pharmacological inhibition of FAK and JNK signaling in human gingival fibroblasts. In vivo, mRNA levels for fibronectin peaked at day 3 and 7 post wounding, with protein immunoreactivity highest at day 7, suggesting periostin is a modulator of fibronectin production during gingival healing.
在皮肤愈合过程中，骨膜蛋白通过β1 整合素/FAK 依赖机制促进肌成纤维细胞分化，并且持续表达与瘢痕形成有关。与皮肤不同，牙龈组织在受伤后通常不会形成瘢痕，但骨膜蛋白在牙龈愈合中的作用从未被研究过。使用大鼠牙龈切除术模型，我们表明，在受伤后 14 天内，牙龈结构得以重建。骨膜蛋白 mRNA 水平在受伤后第 7 天达到峰值，在第 14 天连接组织中仍存在骨膜蛋白蛋白。胶原 I 和赖氨酰氧化酶 mRNA 水平在受伤后第 7 天达到峰值，与成纤维细胞增殖的峰值相对应。尽管组织中α-平滑肌肌动蛋白 mRNA 水平增加了 200 倍，但在再生组织中未检测到肌成纤维细胞。在体外，人牙龈成纤维细胞在骨膜蛋白上的黏附，但不是在胶原蛋白上的黏附，被阻断β1 整合素所抑制。在骨膜蛋白上培养的成纤维细胞表现出与仅在胶原蛋白上培养的细胞相似的增殖和肌成纤维细胞分化率。然而，在存在骨膜蛋白的情况下培养的人牙龈成纤维细胞表现出显著增加的纤连蛋白和胶原 mRNA 水平。在人牙龈成纤维细胞中，通过药理学抑制 FAK 和 JNK 信号通路，可减弱纤连蛋白产生的增加。在体内，纤连蛋白的 mRNA 水平在受伤后第 3 天和第 7 天达到峰值，蛋白免疫反应性在第 7 天最高，表明骨膜蛋白是牙龈愈合过程中纤连蛋白产生的调节剂。
