Expression and localization of activin receptors during endochondral bone development

The expression and localization of activins (dimeric protein of inhibin bet a subunit) and activin receptors in skeletal tissue were examined. RT-PCR r evealed that cultured chondrocytes expressed mRNAs of inhibin/activin beta (A) and four activin receptors (two type I (ActRI and ActRIB) and two type II (ActRII and ActRIIB)). Immunohistochemical analyses showed that activin beta (A), ActRI and ActRII were localized in proliferating chondrocytes and osteoblasts in tibiae of neonatal rats, and in implants of demineralized b one matrix, a well-established model of ectopic bone formation. The immunor eactivities of osteoblasts were decreased with aging in the tibiae and with progressing endochondral bone development in the implants. The strong expr ession of ActRI was also detected in hypertrophic chondrocytes both in the tibial growth plate and in the implants, whereas immunoreactive ActRII was lower in hypertrophic chondrocytes, Western blot analysis also showed that immunoreactive ActRI, migrating at 52 kDa, was detected only in the implant s on days 9 and 11, the period of conversion from cartilage to bone. In vie w of the sharing of type II receptors between activins and bone morphogenet ic proteins (BMPs), our findings suggest that activin/BMP activity involves in bone modeling, especially during active chondro- and osteogenesis and d uring the conversion from cartilage to bone.