The differences between oral mucosa and skin wound healing involving hypoxic responses of fibroblasts are poorly elucidated. In this study, we aimed to study the different hypoxic responses between oral and skin fibroblasts embedded in a three-dimensional (3D) collagen matrix to address the early stage of wound healing. Primary oral mucosa fibroblasts (OMFs) obtained from the retromolar area and skin fibroblasts (SFs) obtained from the abdomen were cultured in the 3D ‘floating model’ under either 21%, 5% or 1% O₂ for 2 days. Cell viability under hypoxia was higher in the OMFs than in the SFs. Collagen gel contraction was suppressed under hypoxic conditions in both fibroblasts, consistent with the reduction of alpha smooth muscle actin expression, except for SFs under 1% O₂. Subsequently, their gene expression profiles between 21 and 1% O₂ concentrations were compared via microarray technology, and the expression profiles of the extracellular matrix (ECM)-associated proteins, including matrix metalloproteinases and collagens, were evaluated. The OMFs were more susceptible to 1% O₂, and more of their genes were downregulated than the SFs’. Although the production and expression levels of ECM-associated proteins in both fibroblasts diminished under hypoxia, those levels in OMFs were significantly higher than those in SFs. In the case of single origin OMFs and SFs, our findings suggest that OMFs possess a higher baseline production capacity of several ECM-associated proteins than SFs, except type III collagen. The intrinsic hypoxic responses of OMFs may be attributed to a more favourable wound healing in oral mucosa.

口腔黏膜和皮肤伤口愈合之间的差异涉及成纤维细胞的低氧反应，目前尚不清楚。在这项研究中，我们旨在研究嵌入在三维（3D）胶原蛋白基质中的口腔和皮肤成纤维细胞之间的不同低氧反应，以解决伤口愈合的早期阶段。在3D“漂浮模型”中，将在后磨牙区获得的原发口腔黏膜成纤维细胞（OMF）和从腹部获得的皮肤成纤维细胞（SF）在21％，5％或1％O _2下培养2天。在缺氧条件下，OMFs中的细胞活力高于SFs。在缺氧条件下，两种成纤维细胞均抑制胶原蛋白凝胶收缩，这与α平滑肌肌动蛋白表达的降低相一致，但SFs低于1％O ₂除外。随后，通过微阵列技术比较了它们在21％和1％O ₂浓度之间的基因表达谱，并评估了细胞外基质（ECM）相关蛋白（包括基质金属蛋白酶和胶原蛋白）的表达谱。OMF更容易受到1％O _2的影响，并且比SF的基因被下调的更多。尽管在缺氧条件下，两种成纤维细胞中ECM相关蛋白的产生和表达水平均降低，但OMF中的这些水平显着高于SF中的水平。对于单一来源的OMF和SF，我们的研究结果表明，除III型胶原蛋白外，OMF与SFs相比，具有几种与ECM相关的蛋白质更高的基线生产能力。OMF的内在缺氧反应可能归因于口腔粘膜更有利的伤口愈合。