INCREASED BONE-FORMATION AND OSTEOBLASTIC CELL PHENOTYPE IN PREMATURECRANIAL SUTURE OSSIFICATION (CRANIOSYNOSTOSIS)

Craniosynostosis is a heterogeneous disorder characterized by prematur e fusion of the skull bone sutures, To evaluate the pathogenesis of pr emature cranial suture ossification in craniosynostosis, we have evalu ated the histologic indices of bone formation and the characteristics of osteoblastic cells derived from normal and affected cranial sutures in 47 infants and children, aged 3-18 months, with nonsyndromic crani osynostosis. The histomorphometric analysis of normal and fused suture s showed an age-related decline in the extent of endosteal bone surfac e covered with osteoid and osteoblasts during postnatal suture ossific ation, Bone formation was 20-50% higher at 3-6 months of age in fused sutures compared,vith normal sutures in the same patients, Cells deriv ed from normal and fused sutures displayed characteristics of the oste oblast phenotype in culture, Analysis of [H-3] thymidine incorporation into DNA from 1-14 days of culture showed an age-related decrease in osteoblastic cell growth in both normal and affected sutures, The prol iferation of osteoblastic cells isolated from fused sutures nas simila r at all ages to that of cells isolated from normal sutures in the sam e patients, In contrast, alkaline phosphatase activity and osteocalcin production by osteoblastic cells cultured in basal conditions and aft er stimulation with 1,25-dihydroxyvitamin D (1,25[OH]D-2(3)), were 53- 74% higher in fused sutures compared with cells isolated from normal s utures in the same patients, The results indicate that bone formation activity at the suture site is locally increased in craniosynostosis, and this disorder is associated with increased in vitro parameters of osteoblastic cell differentiation, suggesting that an increased matura tion of osteoblastic cells at the site of the suture leads to the prem ature ossification in nonsyndromic craniosynostosis.