Function and Regulation of Osteopontin in Response to Mechanical Stress

Abstract

Extensive histological study revealed the impairment of bone remodeling caused by mechanical stress in OPN knockout mice in a tooth movement system. Analysis of OPN promoter transgenic mice showed the mechanical stress response element(s) in the 5.5-kb upstream region. These results were also obtained with the primary cultured cells.Introduction: Mechanical loading system changes the bone architecture through the stimulation of bone remodeling by the action of a numbers of molecules. Among them, we showed that osteopontin (OPN) plays an important role in response to mechanical loading in rats with an experimental system for tooth movement. The results indicate the important role of OPN in bone remodeling. However, the molecular mechanism of OPN expression in response to mechanical stress is unknown. Materials and Methods: OPN knockout mice and transgenic mice carrying green fluorescent protein (GFP) in the control of the OPN promoter were used for analysis. Orthodontic closed coil springs were bonded to the maxillary first molars and incisors for the experimental tooth movement. Spatial expression of GFP and OPN was detected by in situ hybridization. Results: In contrast to wildtype mice, a smaller number of TRACP + cells was detected in OPN knockout mice after treatment. In GFP-OPN5.5 mice, OPN and GFP mRNA-expressing cells were detected in bone cells after treatment, and the localization of GFP was consistent with that of endogenous OPN. An increase in the co-expression of GFP and OPN was detected when primary cultured osteoblastic cells derived from the transgenic mice were exposed to strain or pressure force. Significant increase in the number of OPN + osteocyte was detected in the pressure side at 48 h after treatment. At 72 h, increase in the number of TRACP + cells was detected predominantly in the pressure side. Conclusions: Bone remodeling in response to mechanical stress was suppressed in OPN knockout mice. These results indicate the critical role of OPN in the process of bone remodeling. The analysis of GFP expression in the promoter transgenic mice indicated the presence of an in vivo mechanical stress response element in the 5.5-kb upstream region of the OPN gene.

Upregulation of elastase proteins results in aortic dilatation in mucopolysaccharidosis I mice

“…In addition, the osteopontin promoter contains a PEA3 binding site [41], and osteopontin mRNA was 16-fold normal in MPS I mice. PU.1 is an ets family transcription factor that acts synergistically with IRF-8 to induce expression of genes [42], and is expressed in VSMC [43] and regulates cathepsin S and osteopontin expression.…”

Localization of osteopontin and osterix in periodontal tissue during orthodontic tooth movement in rats

“…Appliance-driven tooth movement models have contributed several key findings relative to the function of osteopontin (OPN) during bone remodeling. [5][6][7] OPN is a major noncollagenous bone matrix glycoprotein that is sialic acid rich and phosphorylated. It was originally isolated from bone and contains an Arg-Gly-Asp (RGD) motif that promotes cell attachment through integrins and CD4.…”

“…6 OPN is thought to promote or regulate the adhesion, attachment, and spreading of osteoclasts to the bone surface during bone resorption. 8 During tooth movement, mechanical stress stimulates osteocytes to express OPN to initiate bone remodeling, 6,7,9 resulting in bone resorption and bone apposition. 5 It is also known to be produced by osteoblasts [10][11][12] and osteoclasts 11,13 as well as osteocytes 6 and is considered to play important roles in bone formation, resorption, and remodeling.…”

Biochemical markers of bone metabolism in gingival crevicular fluid during early orthodontic tooth movement

“…1 Using both in vivo [2][3][4][5] and in vitro 6,7 studies, investigators have tried to elucidate the molecular patterns associated with orthodontic tooth movements in animals and humans. As a result, signaling pathways responsible for bone resorption and bone formation have recently been elucidated.…”