DURA-MATER MAINTAINS RAT CRANIAL SUTURES IN-VITRO BY REGULATING SUTURE CELL-PROLIFERATION AND COLLAGEN PRODUCTION

Craniosynostosis, the premature osseous obliteration of cranial vault sutures, can result from mutations in genes encoding components of gro wth factor signaling systems or the extracellular matrix (ECM). Little is known of the capacity of osteoprogenitor cells of the cranial sutu res to divide or to synthesize ECM in situ. Osteoblasts derived from p atients with prematurely fused sutures were reported to express alkali ne phosphatase and osteocalcin at elevated levels, while proliferating at a rate comparable to control cells [DePollack et al., JBMR, 1996]; however, the suture osteoprogenitors, the population most likely to s how proliferative abnormalities, were not present in the fused sutures used for this study. A model in which rat coronal sutures and associa ted bones develop normally in vitro, but in which sutures can be induc ed to fuse in the absence of dura mater, was used to examine cell prol iferation and total protein synthesis in unfused sutures cultured in t he presence of dura mater or in sutures induced to fuse in the absence of dura mater. Significantly increased cell proliferation was seen in suture cells prior to sutural obliteration, which returned to control levels as sutural fusion proceeded. Collagen synthesis in fusing sutu res was elevated compared to non-fusing sutures and comparable to that seen in bone. Results indicated that in the absence of intercellular signals provided by the dura mater, suture cell proliferation increase d initially, followed by increased synthesis of collagenous ECM within the suture and subsequent osseous obliteration of the suture. Thus fa ctors originating in the dura mater affected suture cell proliferation and ECM production and were required for the maintenance of suture pa tency.