IMMUNOLOCALIZATION OF TRANSFORMING GROWTH-FACTOR-BETA-1, BETA-2, AND BETA-3 AND INSULIN-LIKE GROWTH-FACTOR-I IN PREMATURE CRANIAL SUTURE FUSION

The etiology of craniosynostosis remains unknown. The beta group of tr ansforming growth factors (TGF-P) and insulin-like growth factors (IGF -I and IGF-II) are known to induce new bone formation and, when added exogenously, cause accelerated closure of calvarial defects. The possi ble roles of these bone growth factors in premature cranial suture fus ion in humans have not been explored. We analyzed a total of 20 crania l suture biopsy samples (10 synostotic and 10 normal) from 10 infants with single-suture craniosynostosis undergoing cranial vault remodelin g. Using isoform-specific antibodies for TGF-beta 1, -beta 2, and -bet a 3 and IGF-I, we demonstrated immunoreactivity of these growth factor s in both the craniosynostotic and control suture samples. The results show that these bone growth factors were present in human cranial sut ures; the TGF-beta 2 isoform was the most intensely immunoreactive. Mo st importantly, the TGF-beta isoforms and IGF-I showed more intense im munoreactivity in the actively fusing craniosynostotic sutures compare d with the control patent sutures. Specifically, the TGF-beta isoforms and IGF-I were intensely localized in the osteoblasts synthesizing ne w bone at the suture margin. It is noteworthy that although the patent sutures were less immunoreactive for TGF-beta isoforms than fused sut ures, there was a distinct pattern of the TGF-beta 3 isoform that was immunolocalized to the margin of the normal patent sutures. This sugge sts a possible role for TGF-beta 3 in maintaining cranial suture paten cy. The increased immunoreactivity of both TGF-beta 2 and IGF-I in the actively fusing sutures compared with the patent control sutures indi cates that these growth factors may play a role in the biology underly ing premature suture closure. To our knowledge, this is the first stud y showing the presence of TGF-beta 1, -beta 2, and -beta 3 and IGF-I i n prematurely fusing human cranial sutures. In the future, manipulatin g the local expression of these growth factors at the suture site may enable plastic surgeons to modulate premature suture fusion.