Horner A, Kemp P, Summers C, Bord S, Bishop N J, Kelsall A W, Coleman N, Compston J E
Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, UK.
Bone. 1998 Aug;23(2):95-102. doi: 10.1016/s8756-3282(98)00080-5.
Transforming growth factors type beta (TGF-beta1, -beta2, and -beta3) are potent stimulators of bone formation and have been shown to regulate chondrocyte, osteoblast, and osteoclast formation and function. However, the distribution of the different isoforms and their signaling receptors in human bone in vivo has not previously been reported. Using samples of normal (neonatal rib) and pathological (osteophytic) developing human bone, we have investigated the expression of the different TGF-beta isoforms and their signaling receptors (TGF-betaRI and RII) at the messenger ribonucleic acid (mRNA) and protein levels by in situ hybridization and immunolocalization to establish the sites of TGF-beta production and their possible sites of action during human bone development in vivo. All three TGF-beta isoforms and the receptors were detected at sites of endochondral and intramembranous ossification. At sites of endochondral ossification, TGF-beta2 was detected in all zones of the cartilage, with the highest expression seen in the hypertrophic and mineralizing zones. TGF-beta3 was detected in proliferative and hypertrophic zone chondrocytes, while TGF-beta1 expression was restricted to the proliferative and upper hypertrophic zones. TGF-betaRI and RII exhibited similar distributions with maximum expression in the hypertrophic and mineralizing zones in the neonatal rib but in the resting/proliferative zone in the developing osteophyte. At sites of intramembranous ossification TGF-beta3 was the most widely distributed isoform and showed both matrix- and cell-associated staining. TGF-beta2 and -beta1 were expressed almost exclusively at sites of mineralization. These observations demonstrate that the different TGF-beta isoforms and their receptors exhibit distinct but overlapping patterns of expression, and support the hypothesis that they are involved in the regulation of endochondral and intramembranous ossification during human bone development in vivo.
转化生长因子β型（TGF-β1、-β2和-β3）是骨形成的强效刺激因子，已被证明可调节软骨细胞、成骨细胞和破骨细胞的形成及功能。然而，此前尚未有关于不同异构体及其信号受体在人骨体内分布的报道。我们使用正常（新生儿肋骨）和病理性（骨赘）发育中的人骨样本，通过原位杂交和免疫定位技术，在信使核糖核酸（mRNA）和蛋白质水平上研究了不同TGF-β异构体及其信号受体（TGF-βRI和RII）的表达情况，以确定TGF-β在人骨体内发育过程中的产生部位及其可能的作用位点。在软骨内成骨和膜内成骨部位均检测到了所有三种TGF-β异构体和受体。在软骨内成骨部位，在软骨的所有区域均检测到TGF-β2，在肥大和矿化区域表达最高。在增殖和肥大区域的软骨细胞中检测到TGF-β3，而TGF-β1的表达仅限于增殖和上部肥大区域。TGF-βRI和RII表现出相似的分布，在新生儿肋骨的肥大和矿化区域表达最高，但在发育中的骨赘的静止/增殖区域表达最高。在膜内成骨部位，TGF-β3是分布最广泛的异构体，显示出与基质和细胞相关的染色。TGF-β2和-β1几乎仅在矿化部位表达。这些观察结果表明，不同的TGF-β异构体及其受体表现出不同但重叠的表达模式，并支持它们参与人骨体内发育过程中软骨内成骨和膜内成骨调节的假说。
