Osterix is a key target for mechanical signals in human thoracic ligament flavum cells

Fan, Dongwei; Chen, Zhongqiang; Wang, Dan; Guo, Zhixin; Qi, Qiang; Shang, Yongfeng

doi:10.1002/jcp.21016

Cited by 51 publications

(41 citation statements)

References 32 publications

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“…OPN reactivity in the cement line and surface of cementum and alveolar bone might be induced by osterix expression. Their strong localization in periodontal tissues when 100 g of heavy force was applied indicates that they might be molecules linking mechanostressing and osteogenic and odontogenic differentiation 20,23,24 and might be involved in bone, PDL, and cementum remodeling during orthodontic tooth movement. The precise relationship between OPN and osterix during periodontal tissue remodeling in response to heavy force could not be ascertained with the current methodology.…”

Section: Discussionmentioning

confidence: 99%

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

Kim

Jue

et al. 2011

The Angle Orthodontist

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Objective: To evaluate the localization of osteopontin (OPN) and osterix in periodontal tissue during experimental tooth movement with heavy force in rats. Materials and Methods: Nickel-titanium closed-coil springs were used to create a 100 g mesial force to the maxillary first molars. On days 3, 7, 10, and 14 after force application, histological changes in periodontium were examined by immunohistochemistry using proliferating cell nuclear antigen (PCNA), OPN, and osterix. Results: PCNA-positive cells were found close to the alveolar bone and cementum on both sides. OPN-positive cells were observed along the cementing line of the cementum and bone on both sides and also were visible along with newly formed fibers in the periodontal ligament on the tension side. Osterix-positive cells were strongly detected on the surface of the alveolar bone and cementum on both sides. Conclusions: During tooth movement, periodontal remodeling occurs on both sides. These results indicate that OPN and osterix may play an important role of differentiation and osteoblasts and cementoblasts matrix formation during periodontal tissue remodeling.

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Section: Discussionmentioning

confidence: 99%

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

Kim

Jue

et al. 2011

The Angle Orthodontist

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“…Recent studies have demonstrated that the activation of MAPK signaling cascade contributes to osteogenic differentiation of cultured LFCs induced by mechanical stress and leptin, which were considered as the causes of OLF [25,43]. However, whether the activation of ERK1/2 and p38 MAPK is involved in rhGDF-5 induced LFCs differentiation need to be further studied.…”

Section: Discussionmentioning

confidence: 99%

Growth/differentiation Factor-5 Induces Osteogenic Differentiation of Human Ligamentum Flavum Cells through Activation of ERK1/2 and p38 MAPK

Zhong

Chen

Zhang

et al. 2010

Cell Physiol Biochem

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Ossification of ligamentum flavum (OLF) is a pathological ectopic ossification in the spinal ligament, leading to spinal canal stenosis, but little was known about its pathogenesis. A previous study has found growth/differentiation factor (GDF)-5 expression at ossified sites of the ligaments from OLF patients. This study aimed to investigate the osteogenic effects of GDF-5 on cultured human ligamentum flavum cells (LFCs). LFCs were isolated from human spinal ligamentum flavum, and treated with or without recombinant human (rh) GDF-5. Alkaline phosphatase (ALP) activity was measured. Expression of osteocalcin was assessed by reverse transcriptase-PCR, Western blotting and immunofluorescence. Matrix mineralization was assessed by alizarin red staining. Activation of mitogen-activated protein kinases (MAPK) ERK1/2, p38 and JNK were detected by Western blotting. We found that rhGDF-5 treatment increased ALP activity and osteocalcin expression in a time-and dosedependent manner, and induced mineralized nodule form. In addition, rhGDF-5 challenge mediated the ERK1/2 and p38 activation but not JNK. Inhibiting this activation pharmacologically, using U0126, a ERK1/ 2 inhibitor, or SB203580, a p38 inhibitor, resulted in significantly lower ALP activity and osteocalcin protein expression. The present study shows that rhGDF-5 induces osteogenic differentiation of human LFCs through activation of ERK1/2 and p38 MAPK. These findings give some new insight into the pathogenesis of OLF.

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“…For instance, activation of p38 MAPK by BMP-2 has been shown to be relevant in the osteogenic effects of this cytokine (38 -40). Furthermore, the inhibition of the p38 pathway strongly inhibits Osx expression induced by BMP-2, insulinlike growth factor-I, or mechanical stress (41)(42)(43). Thus, we analyzed whether Dlx5 could be a target of the p38 pathway.…”

Section: Volume 283 • Number 7 • February 15 2008mentioning

confidence: 99%

BMP-2 Induces Osterix Expression through Up-regulation of Dlx5 and Its Phosphorylation by p38

Ulsamer

Ortuño

Ruiz

et al. 2008

Journal of Biological Chemistry

193

187

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Osterix, a zinc-finger transcription factor, is specifically expressed in osteoblasts and osteocytes of all developing bones. Because no bone formation occurs in Osterix null mice, Osterix is thought to be an essential regulator of osteoblast differentiation. We report that bone morphogenetic protein-2 (BMP-2) induces an increase in Osterix expression, which is mediated through a homeodomain sequence located in the proximal region of the Osterix promoter. Our results demonstrate that induction of Dlx5 by BMP-2 mediates Osterix transcriptional activation. First, BMP-2 induction of Dlx5 precedes the induction of Osterix. Second, Dlx5 binds to the BMP-responsive homeodomain sequences both in vitro and in vivo. Third, Dlx5 overexpression and knock-down assays demonstrate its role in activating Osterix expression in response to BMP-2. Furthermore, we show that Dlx5 is a novel substrate for p38 MAPK in vitro and in vivo and that Ser-34 and Ser-217 are the sites phosphorylated by p38. Phosphorylation at Ser-34/217 increases the transactivation potential of Dlx5. Thus, we propose that BMP activates expression of Osterix through the induction of Dlx5 and its further transcriptional activation by p38-mediated phosphorylation.Bone is a dynamic tissue that is constantly remodeled throughout life. Bone remodeling activity is dependent on a strict coupling mechanism of osteoclast resorption and new matrix deposition by osteoblasts, and an imbalance between these two activities leads to pathological states such as osteoporosis and osteosclerosis. Commitment to the osteoblast phenotype is ultimately controlled by a specific set of transcription factors activated by signals and regulatory pathways. Among them, bone morphogenetic protein (BMP) 5 signaling has been shown to be involved in bone regeneration and osteoblast differentiation in vitro and in vivo (1-3). BMP target genes include a growing number of tissue-determining transcription factors that promote differentiation of mesenchymal precursors toward the osseous cell phenotypes. For instance, osteogenic induction of bone marrow mesenchymal stem cells or premyogenic C2C12 cells has identified several types of transcription factors such as Id1, several homeodomain proteins, ATF4, the runt homology domain factor Runx2 (Cbfa1) and Osterix (Osx) (for review, see Refs. 4 -6). Runx2 and Osx have been widely accepted as master osteogenic factors since neither Cbfa1 nor Osx null mice form mature osteoblasts (7,8). Nakashima et al. (8) identified Osx as a zinc-finger SP1 family member induced by BMP-2 in C2C12 cells that is specifically expressed in osteoblasts and osteocytes of all developing bones. In Osx-null mice, no bone formation takes place, although Runx2 is expressed, suggesting that Osx acts downstream of Runx2 during bone development (8). It has been suggested that Runx2 would function from the commitment step to the point where osteochondroprogenitors appear, whereas Osx would have a role in the segregation of osteoblasts from osteochondroprogenitors (5). Supporting ...

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Osterix is a key target for mechanical signals in human thoracic ligament flavum cells

Cited by 51 publications

References 32 publications

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

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

Growth/differentiation Factor-5 Induces Osteogenic Differentiation of Human Ligamentum Flavum Cells through Activation of ERK1/2 and p38 MAPK

BMP-2 Induces Osterix Expression through Up-regulation of Dlx5 and Its Phosphorylation by p38

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