Bone regeneration originates from proliferation and differentiation of osteoprogenitors via either endochondral or intramembranous ossification; and the regeneration capacities decline with age and estrogen loss. Maxillary sinus floor lifting (MSFL) is a commonly used surgical procedure for guiding bone regeneration in maxilla. Radiographic analysis of 1210 clinical cases of maxilla bone regeneration after MSFL revealed that the intrasinus osteogenic efficacy was independent of age and gender, however; and this might be related to the Schneiderian membrane that lines the sinus cavity. In view of the particularity of this biological process, our present study aimed to elucidate the underlying mechanism of MSFL-induced bone regeneration. We first established a murine model to simulate the clinical MSFL. By single-cell RNA-sequencing and flow cytometry-based bulk RNA-sequencing, we identified a novel Krt14⁺Ctsk⁺ subset of cells that display both epithelial and mesenchymal properties and the transcriptomic feature of osteoprogenitors. Dual recombinases-mediated lineage tracing and loss-of-function analyses showed that these Krt14⁺Ctsk⁺ progenitors contribute to both MSFL-induced osteogenesis and physiological bone homeostasis by differentiating into Krt14^–Ctsk⁺ descendants which show robust osteogenic capacity. In addition, we detected a similar population of Krt14⁺Ctsk⁺ cells in human samples of Schneiderian membrane, which show a highly similar osteogenic potential and transcriptomic feature to the corresponding cells in mice. The identification of this Krt14⁺Ctsk⁺ population, featured by osteoprogenitor characteristics and dual epithelial–mesenchymal properties, provides new insight into the understanding of bone regeneration and may open more possibilities for clinical applications.

骨再生源于骨祖细胞通过软骨内或膜内骨化的增殖和分化；再生能力随着年龄和雌激素的流失而下降。上颌窦底提升术 (MSFL) 是一种常用的引导上颌骨骨再生的外科手术。然而，对 1210 例 MSFL 后上颌骨再生临床病例的放射学分析显示，窦内成骨效果与年龄和性别无关；这可能与排列在窦腔内的 Schneiderian 膜有关。鉴于这一生物学过程的特殊性，我们目前的研究旨在阐明 MSFL 诱导骨再生的潜在机制。我们首先建立了小鼠模型来模拟临床 MSFL。Krt14 ⁺ Ctsk ⁺显示上皮和间充质特性以及骨祖细胞转录组学特征的细胞子集。双重组酶介导的谱系追踪和功能丧失分析表明，这些Krt14 ⁺ Ctsk ⁺祖细胞通过分化为显示出强大成骨能力的Krt14 ^– Ctsk ⁺后代，有助于 MSFL 诱导的成骨和生理性骨稳态。此外，我们检测到类似的Krt14 ⁺ Ctsk ⁺人类施耐德氏膜样本中的细胞，显示出与小鼠相应细胞高度相似的成骨潜力和转录组学特征。这种以骨祖细胞特征和上皮-间充质双重特性为特征的Krt14 ⁺ Ctsk ⁺群体的鉴定，为对骨再生的理解提供了新的见解，并可能为临床应用开辟更多可能性。