Oshin A O, Stewart M C
Department of Veterinary Clinical Medicine, University of Illinois at Urbana-Champaign, 1008 West Hazelwood Drive, Urbana, IL 61802, USA.
Vet Comp Orthop Traumatol. 2007;20(3):151-8. doi: 10.1160/vcot-07-02-0018.
Bone morphogenetic proteins (BMPs) are members of the TGF-beta superfamily of secreted ligands. BMPs regulate a diverse range of developmental processes during embryogenesis and postnatal development, and control the differentiation of several musculoskeletal tissues including bone, cartilage, tendon and ligaments. The ability of BMPs to modulate the phenotype of cells in these tissue lineages suggests that these factors could be valuable for musculoskeletal tissue regeneration. In fact, BMPs-2 and -7 are already in clinical use for bone regeneration. This review addresses the signaling mechanisms by which BMPs regulate cellular processes, the role of BMPs in articular cartilage development and joint formation, and the data that supports the use of BMPs for in vitro phenotypic support of articular chondrocyte cultures, chondrogenic differentiation of mesenchymal stem cells (MSCs) and articular cartilage repair. Given the documented importance of BMP activity for normal joint formation, articular cartilage development and maintenance, the chondrogenic activity of BMPs when applied to MSC cultures and the encouraging outcomes of several in vivo cartilage repair studies, BMP therapies hold considerable promise for effective cartilage repair and/or regeneration. Future advances in the control of BMP elution from biocompatible matrices and prolonged, dose-controlled BMP expression by genetically engineered cells should substantially improve cartilage repair strategies using BMPs and similar chondro-protective proteins.
骨形态发生蛋白(BMPs)是分泌型配体TGF-β超家族的成员。BMPs在胚胎发生和出生后发育过程中调节多种发育过程,并控制包括骨、软骨、肌腱和韧带在内的几种肌肉骨骼组织的分化。BMPs调节这些组织谱系中细胞表型的能力表明,这些因子对肌肉骨骼组织再生可能具有重要价值。事实上,BMP-2和BMP-7已在临床上用于骨再生。本综述探讨了BMPs调节细胞过程的信号传导机制、BMPs在关节软骨发育和关节形成中的作用,以及支持使用BMPs进行关节软骨细胞培养的体外表型支持、间充质干细胞(MSCs)的软骨形成分化和关节软骨修复的数据。鉴于BMP活性对正常关节形成、关节软骨发育和维持的重要性已得到证实,BMPs应用于MSC培养时的软骨形成活性以及多项体内软骨修复研究令人鼓舞的结果,BMP疗法在有效软骨修复和/或再生方面具有很大的前景。在控制BMP从生物相容性基质中洗脱以及通过基因工程细胞实现BMP的长期、剂量可控表达方面的未来进展,应能大幅改善使用BMPs和类似软骨保护蛋白的软骨修复策略。