Expression and distribution of transforming growth factor-β isoforms and their signaling receptors in growing human bone

Transforming growth factors type beta (TGF-beta 1, -beta 2, and -beta 3) 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 hone in vivo has not previously been reported. Using samples of normal (neonatal rib) and pathological (osteophytic) developing human bene,,ve have investigated the expression of the different TGF-beta isoforms and their signaling receptors (TGF-beta RI 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, AIL three TGF-beta isoforms and the receptors were detected at sites of endochondral and intramembranous ossification. At sites of endochondral ossification, TGF-beta 2 was detected in ail zones of the cartilage, with the highest expression seen in the hypertrophic and mineralizing zones. TGF-beta 3 was detected in proliferative and hypertrophic zone chondrocytes, while TGF-beta 1 expression was restricted to the proliferative and upper hypertrophic zones. TGF-beta RI 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-beta 3 was the most widely distributed isoform and shelved both matrix- and cell-associated staining. TGF-beta 2 and -beta 1 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, (Bone 23:95-102; 1998) (C) 1998 by Elsevier Science Inc, All rights reserved.