Articular cartilage contains an extracellular matrix with characteristic macromolecules such as type II collagen. Because this tissue is avascular and mature chondrocytes do not proliferate, cartilage lesions have a limited capacity for healing after trauma. Autologous chondrocyte implantation (ACI) is widely used for the treatment of patients with focal damage to articular cartilage. However, this method faces a major issue: dedifferentiation of chondrocytes occurs during the long-term culture necessary for mass cell production. The aim of this study was to determine if the step of cell amplification required for ACI could benefit from the use of bone morphogenetic protein (BMP)-2, a potent regulator of chondrogenic expression. Chondrocytes were isolated from human nasal cartilage, a hyaline cartilage like articular cartilage and were serially cultured in monolayers. After one, two or three passages, BMP-2 was used to evaluate the chondrogenic potential of the dedifferentiated chondrocytes, at the gene and protein level. We found that BMP-2 can reactivate the program of chondrogenic expression in dedifferentiated chondrocytes. To gain insight into the molecular mechanisms involved in the responsiveness of chondrocytes to BMP-2, we examined the phosphorylation of Smad proteins and the interaction of the Sry-type high-mobility-group box (Sox) transcription factors with the cartilage-specific enhancer of the type II procollagen gene. Our results show that BMP-2 acts by stimulating Smad phosphorylation and by enhancing DNA-binding of the Sox transcription factors to the specific enhancer of the type II procollagen gene. Thus, this study reveals the potential use of BMP-2 as a stimulatory agent in conventional ACI strategies.

中文翻译：

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骨形态发生蛋白2刺激体外扩增的人鼻软骨细胞中的软骨形成表达。

关节软骨包含具有特征性大分子（例如II型胶原）的细胞外基质。因为该组织是无血管的并且成熟的软骨细胞不会增殖，所以软骨损伤在创伤后的愈合能力有限。自体软骨细胞植入（ACI）被广泛用于治疗关节软骨局灶性损伤的患者。然而，该方法面临一个主要问题：软骨细胞的去分化发生在大规模细胞生产所必需的长期培养过程中。这项研究的目的是确定ACI所需的细胞扩增步骤是否可以受益于软骨形成表达的有效调节剂骨形态发生蛋白（BMP）-2。软骨细胞是从人鼻软骨中分离出来的，像关节软骨一样的透明软骨，连续培养成单层。经过一，两或三次传代后，在基因和蛋白质水平上，使用BMP-2评估去分化软骨细胞的软骨形成潜能。我们发现BMP-2可以重新激活去分化软骨细胞中的软骨表达程序。为了深入了解软骨细胞对BMP-2应答的分子机制，我们研究了Smad蛋白的磷酸化以及Sry型高迁移率族框（Sox）转录因子与软骨特异性增强子的相互作用。 II型原胶原基因的表达。我们的结果表明，BMP-2通过刺激Smad磷酸化并通过增强Sox转录因子与II型原胶原基因特异性增强子的DNA结合而起作用。从而，