Comparative study of the in vitro characteristics of osteoblasts from paralytic and non-paralytic children

Abstract

Study design: Cerebral palsy is known to provoke a high loss of bone in children and adults. The potential interest of human osteoblastic cell culture for assessing the osteoblastic function in metabolic bone disorders has been demonstrated by many previous studies. Few studies have attempted to evaluate the capacities of osteoblasts isolated from immobilized or normal bones by in vitro culture methods. Moreover, a few teams did make the distinction between young spastic and¯accid patients. Objectives: We attempted to characterize mature osteoblasts (OB) and bone marrow-stromal cells (BM) originating from 56 immobile and normal children. Spastic and¯accid patients formed the paralytic group. Setting: France. Methods: Osteoblasts and bone marrow cells were isolated from iliac crests obtained during pelvic osteotomies of young control and paralytic patients. The in vitro viability, proliferation and di erentiation parameters of the cells from paralytic patients were compared with those of cells coming from normal controls. Results: No signi®cant di erences in the cell proliferation parameters were observed between the two groups. Only initial cell viability before inoculation was lower for the paralytic group, compared to the control group. On the other hand, contrary to expectations, we found that fresh and thawed OB cells from¯accid patients synthesized more osteocalcin and more collagen respectively than those of the spastic and control groups. Opposite results were obtained from BM cultures. Conclusion: A negative feedback mechanism by systemic or local factors, which is not conserved in vitro but controls the in vivo osteocalcin and collagen synthesis of¯accid paralytic OB cells, is hypothesized. Because these¯accid patients are known to have a high fat/lean mass, we suggest that leptin may be the potential regulating factor implicated in the hypothesized negative feedback mechanism. Spinal Cord (2000) 38, 622 ± 629

Leptin stimulates human osteoblastic cell proliferation, de novo collagen synthesis, and mineralization: Impact on differentiation markers, apoptosis, and osteoclastic signaling

“…Leptin administration leads to a significant increase in femoral length, total body area, as well as bone mineral content and bone density [Liu et al, 1997;Matkovic et al, 1997;Iwaniec et al, 1998;. Other reports, however, assert that leptin inhibits bone formation through a central nervous regulatory loop [Anselme et al, 2000;Ducy et al, 2000;Fleet, 2000], claiming that there is no leptin signaling in osteoblastic cells. Our findings are substantiated by the very recent report by Bassilana et al (2000), demonstrating that human mesenchymal stem cells, when differentiated, express leptin and leptin receptor isoforms, as well as leptin-induced phosphorylation of STAT3.…”

“…Most importantly, it was shown that leptin preferentially induced differentiation of stromal cells into osteoblasts [Thomas et al, 1999;Marie et al, 2000] and chondrocytes, but also adipocytes [Marie et al, 2000], depending on incubation conditions. However, some researchers [Anselme et al, 2000;Ducy et al, 2000;Fleet, 2000] failed to identify leptin receptors in osteoblasts, and advocate a strict neuroendocrine and indirect regulation of bone metabolism and function by leptin. The contradicting in vivo results provide a need for more investigation.…”

TNF-α and IL-1β inhibit RUNX2 and collagen expression but increase alkaline phosphatase activity and mineralization in human mesenchymal stem cells

“…LeggPerthes-Calve disease is an idiopathic avascular necrosis of the femoral head, which does not affect the iliac crest. Bone marrow was extracted as previously published in details (Anselme et al 2000). Briefly, a small part of the body iliac crest was removed at the end of the surgery in order to close without creating tension of the iliac crest.…”

Effects of Leptin to Cultured Growth Plate Chondrocytes

“…Peripheral influences of leptin on bone remodeling have been reported in adults, but fewer studies have concerned children [14, 15]. The effects of leptin on growth plate chondrocytes have not been described.…”