BMP2 stimulates bone formation and signals preferably through BMP receptor (BMPR) 1A, whereas GDF5 is a cartilage inducer and signals preferably through BMPR1B. Consequently, BMPR1A and BMPR1B are believed to be involved in bone and cartilage formation, respectively. However, their function is not yet fully clarified. In this study, GDF5 mutants with a decreased affinity for BMPR1A were generated. These mutants, and wild-type GDF5 and BMP2, were tested for their ability to induce dimerization of BMPR1A or BMPR1B with BMPR2, and for their chondrogenic, hypertrophic and osteogenic properties in chondrocytes, in the multipotent mesenchymal precursor cell line C3H10T1/2 and the human osteosarcoma cell line Saos-2. Mutants with the lowest potency for inducing BMPR1A–BMPR2 dimerization exhibited minimal chondrogenic and osteogenic activities, indicating that BMPR1A is necessary for chondrogenic and osteogenic differentiation. BMP2, GDF5 and the GDF5 R399E mutant stimulated expression of chondrogenic and hypertrophy markers in C3H10T1/2 cells and chondrocytes. However, GDF5 R399E, which induces the dimerization of BMPR1B and BMPR2 more potently than GDF5 or BMP2, displayed reduced hypertrophic activity. Therefore, we postulate that stronger BMPR1B signaling, compared to BMPR1A signaling, prevents chondrocyte hypertrophy and acts as a cartilage stabilizer during joint morphogenesis.

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BMP2 刺激骨形成并优选通过 BMP 受体 (BMPR) 1A 发出信号，而 GDF5 是软骨诱导剂并优选通过 BMPR1B 发出信号。因此，BMPR1A 和 BMPR1B 被认为分别参与骨和软骨的形成。然而，它们的功能尚未完全阐明。在这项研究中，产生了对 BMPR1A 亲和力降低的 GDF5 突变体。在多能间充质前体细胞系 C3H10T1/2 和人骨肉瘤细胞系Saos-2。诱导 BMPR1A-BMPR2 二聚化能力最低的突变体表现出最小的软骨形成和成骨活性，表明 BMPR1A 对于软骨形成和成骨分化是必需的。BMP2、GDF5 和 GDF5 R399E 突变体刺激 C3H10T1/2 细胞和软骨细胞中软骨形成和肥大标记物的表达。然而，GDF5 R399E 比 GDF5 或 BMP2 更有效地诱导 BMPR1B 和 BMPR2 二聚化，显示出肥大活性降低。因此，我们假设与 BMPR1A 信号相比，更强的 BMPR1B 信号可以防止软骨细胞肥大，并在关节形态发生过程中充当软骨稳定剂。

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