构建组织工程软骨是再生医学的热点。BMP2诱导MSCs成软骨分化，其激发的软骨细胞肥大分化是构建组织工程软骨的瓶颈。我们构建了新型小RNA库探索lncRNA对基因表达的调控，通过该库的筛选和验证，发现lncRNA H19是调控MSCs分化的关键lncRNAs之一。进一步发现过表达H19促进BMP2诱导MSCs生成的软骨细胞增殖，沉默H19促进BMP2诱导MSCs生成的软骨细胞肥大分化，提示H19调控BMP2介导的软骨细胞肥大分化；而软骨细胞的肥大分化主要受Ihh-PTHrP信号调控；故提出BMP2/H19/miR/Ihh-PTHrP调控BMP2介导的软骨细胞肥大分化假说。拟以BMP2介导的软骨细胞肥大分化为节点，以H19的CeRNA调控网络为基础，通过体内外研究阐明上述分子机制，并通过软骨缺损模型验证干预H19通路对软骨缺损修复的影响，为构建基于BMP2的组织工程软骨提供实验和理论基础。

Cartilage tissue engineering are promising in the treatment of cartilaginous pathologies. Bone Morphogenetic Protein 2 (BMP2) hold the capacity to induce Mesenchymal Stem Cells (MSCs) chondrogenic differentiation. However, we found that BMP2 triggered hypertrophic differentiation which blocked the construction of BMP2 mediated cartilage tissue engineering. Recently, to figure out the regulation effect of long non-coding RNA (lncRNA), we successfully constructed a novel short RNA library, which expresses completely randomized 19-mer. Through RNA library screening, we successfully constructed differentiation-resistant cell line, and found that the expression of lncRNA H19 was the lowest among all lncRNAs in differentiation-resistant cell line. Our further research found overexpression of H19 promoted BMP2-induced chondrocytes proliferation, what is more, silencing H19 promoted BMP2-induced chondrocytes hypertrophic differentiation, which indicates H19 regulate BMP2-induced chondrocytes hypertrophic differentiation. Meanwhile, the hypertrophic differentiation process of chondrocyte is regulated by Indian Hedgehog (Ihh) -Parathyroid hormone-related protein (PTHrP) signaling, therefore, we present the regulation hypothesis of BMP2/H19/miR/Ihh-PTHrP. On the basis of lncRNA H19 mediated competing endogenous RNA (CeRNA) mechanism, this project will focus on BMP2 mediated hypertrophic differentiation of chondrocytes, clarify the regulation hypothesis of BMP2/H19/miR/Ihh-PTHrP through in vitro and in vivo experiments, and identify the repair effect of BMP2-H19 mediated tissue engineering cartilage in cartilage defect model. Collectively, this project will provide new theoretical and experimental evidence for BMP2 mediated cartilage tissue engineering.