C. Depollack et al., INCREASED BONE-FORMATION AND OSTEOBLASTIC CELL PHENOTYPE IN PREMATURECRANIAL SUTURE OSSIFICATION (CRANIOSYNOSTOSIS), Journal of bone and mineral research, 11(3), 1996, pp. 401-407
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.