Osteopontin Expression in Osteoblasts and Osteocytes During Bone Formation Under Mechanical Stress in the Calvarial Suture In Vivo

Abstract

To clarify the role of OPN in bone formation under mechanical stress, we examined the expression and the function of OPN in bone using an expansion force-induced osteogenesis model. Our results indicated that OPN expression was enhanced during the bone formation and that OPN would be one of the positive factors for the bone formation under mechanical stress.Introduction: Bone formation is known to be stimulated by mechanical stress; however, molecules involved in stress-dependent regulation of bone formation have not yet been fully characterized. Extracellular matrix proteins such as osteopontin (OPN) could play a role in mediation of the mechanical stress signal to osteoblasts. However, the function of OPN in bone formation under mechanical force is not known. Therefore, we examined the expression and the role of OPN in bone formation in vivo under tensile mechanical stress. Materials and Methods: Sagittal sutures of mice were subjected to expansion mechanical stress by setting orthodontic spring wires, and OPN expression during bone formation within the suture gap was examined. Results: Expansion of the sutures resulted in bone formation at the edges of the parietal bones within the sagittal suture. Immunohistochemical analysis revealed abundant accumulation of OPN protein in the matrix of newly formed bone on the inner edge of the parietal bone within the mechanically expanded sutures. Osteoblasts forming bone within the suture subjected to tensile stress also exhibited high levels of OPN protein expression. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis indicated that OPN mRNA expression was enhanced in wild-type calvariae subjected to expansion force compared with the control calvariae where dead spring wires were set without expansion stress. In addition, type I collagen mRNA was also expressed in the calvariae under the mechanical stimuli. To understand the function of OPN, sagittal sutures in OPN-deficient mice were subjected the expansion stress, and bone formation within the suture to fill the expanded gap was compared with that observed in wild-type mice. OPN deficiency reduced bone formation at the edge of the parietal bone in contact with the expanded suture gap. Conclusions: These observations revealed that OPN plays a pivotal role in bone formation under tensile mechanical stress.

Osteopontin: Role in immune regulation and stress responses

“…OPN has also been described as a stress mediator that is involved in various stress situations such as mechanical stress, oxidative stress and cellular stress (see chapter 1). For example, OPN has been found necessary for mechanical stress-induced bone loss by regulating the ability of osteocytes to respond to mechanical stress (Morinobu et al, 2003;Ishijima et al, 2007).…”

Mechanical Influences on Suture Development and Patency

“…As might be expected, expansion lowers sutural stiffness [29]. Stretching mouse sagittal sutures for 2 weeks caused the upregulation of not only type I collagen, but also alkaline phosphatase and osteopontin, probably by osteoblasts [59]. Thus the defect that results from the widened suture is rapidly ossified and the end result is elongated bone fronts [63].…”

“…Quasi-static tensile loads have been applied in vivo to the sagittal suture of rats and mice [29,[57][58][59], the internasal suture of rabbits [60], and the interpremaxillary and intermaxillary sutures of rats and macaques [61][62][63][64][65]. The latter imitates a common orthodontic treatment, rapid palatal expansion.…”

Estrogen receptor subtype-specific effects on markers of bone homeostasis

“…Classic markers for bone formation are bone-specific alkaline phosphatase (BALP) (Deftos et al 1991), osteocalcin (OC) (Thiede et al 1994), osteopontin (OPN) (Butler 1989, Sodek et al 2000, Morinobu et al 2003 and collagen propeptides (PICP,PINP) (Eberling et al 1992), while serum and urinary levels of telopeptides of collagen type I (CTx, NTx), pyridinoline crosslinks (Pyd, Dpd) and tartrate-resistant acid phosphatase isoform 5b (TRAP5b)…”