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转化生长因子-β(TGF-β)的最新研究进展:来源、类型、功能及其在软骨/骨愈合中的临床应用。

An update on transforming growth factor-β (TGF-β): sources, types, functions and clinical applicability for cartilage/bone healing.

机构信息

Department of Orthodontics and Dentofacial Orthopedics, Bharati Vidyapeeth Dental College and Hospital, Bharati Vidyapeeth Deemed University, Pune, Maharashtra, India.

出版信息

J Cell Physiol. 2011 Dec;226(12):3094-103. doi: 10.1002/jcp.22698.

DOI:10.1002/jcp.22698
PMID:21344394
Abstract

Transforming growth factor-β (TGF-β) has been reviewed for its sources, types of isoforms, biochemical effects on cartilage formation/repair, and its possible clinical applications. Purification of three isoforms (TGF-β-1, β-2 and β-3) and their biochemical characterization revealed mainly their homo-dimer nature, with heterodimers in traces, each monomer comprised of 112 amino acids and MW. of 12 500 Da. While histo-chemical staining by a variety of dyes has revealed precise localization of TGF-β in tissues, immune-blot technique has thrown light on their expression as a function of age (neonatal vs. adult), as also on its quantum in an active and latent state. X-ray crystallographic studies and nuclear magnetic resonance (NMR) analysis have unraveled mysteries of their three-dimensional structures, essential for understanding their functions. Their similarities have led to interchangeability in assays, while differences have led to their specialized clinical applicability. For this purpose, their latent (inactive) form is changed to an active form through enzymatic processes of phosphorylation/glycosylation/transamination/proteolytic degradation. Their functions encompass differentiation and de-differentiation of chondrocytes, synthesis of collagen and proteoglycans (PGs) and thereby maintain homeostasis of cartilage in several degenerative diseases and repair through cell cycle signaling and physiological control. While several factors affecting their performance are already identified, their interplay and chronology of sequences of functions is yet to be understood. For its success in clinical applications, challenges in judicious dealing with the factors and their interplay need to be understood.

摘要

转化生长因子-β(TGF-β)在其来源、同工型种类、对软骨形成/修复的生化作用及其可能的临床应用方面已得到综述。三种同工型(TGF-β-1、β-2 和 β-3)的纯化及其生化特性揭示了它们主要的同源二聚体性质,痕量存在异源二聚体,每个单体由 112 个氨基酸和 12500 Da 的 MW 组成。虽然各种染料的组织化学染色揭示了 TGF-β在组织中的精确定位,但免疫印迹技术揭示了其表达作为年龄(新生儿与成人)的函数,以及在活性和潜伏状态下的数量。X 射线晶体学研究和核磁共振(NMR)分析揭示了它们三维结构的奥秘,这对于理解其功能至关重要。它们的相似性导致了在测定中的可互换性,而差异导致了它们在专门的临床应用中的适用性。为此,通过磷酸化/糖基化/转氨基/蛋白水解降解等酶促过程将其潜伏(非活性)形式转化为活性形式。它们的功能包括软骨细胞的分化和去分化、胶原和蛋白聚糖(PGs)的合成,从而维持几种退行性疾病中软骨的内稳态,并通过细胞周期信号和生理控制进行修复。虽然已经确定了影响其性能的几个因素,但它们的相互作用和功能序列的时间顺序尚待理解。为了在临床应用中取得成功,需要了解明智处理这些因素及其相互作用的挑战。

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