Age-related changes in bone formation, osteoblastic cell proliferation, and differentiation during postnatal osteogenesis in human calvaria

Abstract

We have determined the age-related changes in the growth characteristics and expression of the osteoblast phenotype in human calvaria osteoblastic cells in relation with histologic indices of bone formation during postnatal calvaria osteogenesis. Histomorphometric analysis of normal calvaria samples obtained from 36 children, aged 3 to 18 months, showed an age-related decrease in the extent of bone surface covered with osteoblasts and newly synthesized collagen, demonstrating a progressive decline in bone formation during postnatal calvaria osteogenesis. Immunohistochemical analysis showed expression of type I collagen, bone sialoprotein, and osteonectin in the matrix and osteoblasts, with no apparent age-related change during postnatal calvaria osteogenesis. Cells isolated from human calvaria displayed characteristics of the osteoblast phenotype including alkaline phosphatase (ALP) activity, osteocalcin (OC) production, expression of bone matrix proteins, and responsiveness to calciotropic hormones. The growth of human calvaria osteoblastic cells was high at 3 months of age and decreased with age, as assessed by (3H)-thymidine incorporation into DNA. Thus, the age-related decrease in bone formation is associated with a decline in osteoblastic cell proliferation during human calvaria osteogenesis. In contrast, ALP activity and OC production increased with age in basal conditions and in response to 1,25(OH)2 vitamin D3, suggesting a reciprocal relationship between cell growth and expression of phenotypic markers during human postnatal osteogenesis. Finally, we found that human calvaria osteoblastic cells isolated from young individuals with high bone formation activity in vivo and high growth potential in vitro had the ability to form calcified nodular bone-like structures in vitro in the presence of ascorbic acid and beta-glycerophosphate, providing a new model to study human osteogenesis in vitro.

A multiscale analytical approach for bone remodeling simulations: Linking scales from collagen to trabeculae

“…an increase of vascular porosity) with age is also shown in [46] authors determined microstructural and strength variables of the distal radius of healthy girls by high-resolution peripheral computerized tomography and micro-finite element analysis and quantified low trabecular vBMD and thickness in the distal radius associated with reduced bone strength and increased fracture risk during growth. The aforementioned increase of vascular porosity is also consistent with the decrease of bone formation with increased age between 3 and 18 months, as evidenced by de Pollak et al [47] in terms of histomorphometric indices.…”

Osteal Tissue Macrophages Are Intercalated throughout Human and Mouse Bone Lining Tissues and Regulate Osteoblast Function In Vitro and In Vivo

“…Sites of osteoblast-mediated bone modeling can be readily identified by the presence of mature cuboidal osteoblasts lining bone surfaces and verified by demonstrating that these osteoblasts express the bone matrix protein type I collagen (30) and the mineralization marker osteocalcin (31). Immunohistochemical staining for F4/80 in sagittal long bone sections from 4-wk-old rapidly growing mice showed that F4/80 ϩ OsteoMacs formed a distinctive canopy-like structure over cuboidal osteoblast-like cells on bone surfaces (Fig.…”

Age-related Changes in the Biomolecular Mechanisms of Clvarial Osteoblast Biology Affect Fibroblast Growth Factor-2 Signaling and Osteogenesis

“…The molecular mechanisms underlying this regenerative capacity are still largely unknown (11). Most investigations have focused on the underlying dura mater; however, this study investigated the age-related cellular and molecular differences between juvenile and adult primary osteoblast cultures and has shown a correlation between their states of proliferation, differentiation, and osteogenic potential in vitro.…”

“…Previous studies have focused on the cellular and molecular differences between juvenile and adult dura mater, which are critical to calvarial bone induction. In contrast, few studies have investigated the effects of age on the cellular and molecular differences between juvenile and adult-derived calvarial osteoblasts (11).…”