Naslov
Impairment of Osteoblast lineage Differentiation leads to Increased Osteoclastogenesis in Osteogenesis Imperfecta Murine

Autori
Li, Haitao ; Jiang, Xi ; Delaney, John ; Bilić- Ćurčić, Ines ; Kalinovsky, Judy ; Grcević, Danka ; Lorenzo. Joseph ; Rowe W., David ; Kalajzić, Ivo

Izvornik
American journal of pathology (0002-9440) 176 (2010), 5; 2405-2413

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
osteogenesis imperfecta ; osteoclastogenesis

Sažetak
This study addressed the role of impairment of osteoblastic differentiation as a mechanism underlying pathophysiology of the osteogenesis imperfecta (OI). We hypothesized that combination of impaired osteogenic differentiation with increased bone resorption leads to diminished bone mass. By introducing visual markers of distinct stages of osteoblast differentiation, pOBCol3.6GFP (3.6GFP ; preosteoblast) and pOBCol2.3GFP (2.3GFP ; osteoblast/osteocytes), into the OIM model, we assessed osteoblast maturation and the mechanism of increased osteoclastogenesis. Cultures from oim/oim ; 2.3GFP mice showed a marked reduction of cells expressing GFP relative to +/+ ; 2.3GFP littermates. No significant difference in expression of 3.6GFP between the +/+ and oim/oim mice was observed. Histological analysis of the oim/oim ; 3.6GFP mice showed an increased area of GFP-positive cells lining the endocortical surface compared with +/+ ; 3.6GFP mice. In contrast GFP expression was similar between oim/oim ; 2.3GFP and +/+ ; 2.3GFP mice. These data indicate that the osteoblastic lineage is under continuous stimulation ; however, only a proportion of cells attain the mature osteoblast stage. Indeed, immature osteoblasts exhibit a stronger potential to support osteoclast formation and differentiation. We detected a higher Rankl/Opg ratio and higher expression of TNF-α in sorted immature osteoblasts. In addition, increased osteoclast formation was observed when osteoclast progenitors were cocultured with oim/oim-derived osteoblasts compared with osteoblasts derived from +/+ mice. Taken together, our data indicate that osteoblast lineage maturation is a critical aspect underlying the pathophysiology of OI.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA