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Overexpression of Dlx2 leads to postnatal condyle degradation.

Dai J, Si J, Zhu X, Zhang L, Wu D, Lu J, Ouyang N, Wang X, Shen G - Mol Med Rep (2016)

Bottom Line: The model was constructed and the phenotype observed using gross observation, micro‑CT scan and histological examination.The model determined that overexpression of Dlx2 may lead to postnatal condyle malformation, subchondral bone degradation and irregular histological structure of the condylar cartilage.In addition, the expression of osteocalcin in the condyle region was markedly downregulated, whereas expression of msh homeobox 2 was upregulated.

View Article: PubMed Central - PubMed

Affiliation: Department of Oral and Cranio‑Maxillofacial Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai 200011, P.R. China.

ABSTRACT
Distal-less homeobox 2 (Dlx2), a member of the Dlx family of transcription factors, is important for the development of craniofacial tissues. Previous studies based on knock‑out mutant mice revealed that Dlx2 primarily disturbed the development of tissues from maxillary arch. The present study used a transgenic mouse model to specifically overexpress Dlx2 in neural crest cells in order to investigate the role of Dlx2 overexpression in post‑natal condyle in mice. The model was constructed and the phenotype observed using gross observation, micro‑CT scan and histological examination. The model determined that overexpression of Dlx2 may lead to postnatal condyle malformation, subchondral bone degradation and irregular histological structure of the condylar cartilage. In addition, the expression of osteocalcin in the condyle region was markedly downregulated, whereas expression of msh homeobox 2 was upregulated. The results of the present study suggest that Dlx2 overexpression in cranial neural crest cells would disrupt the development of post‑natal condyle, which demonstrates that the expression level and the spatiotemporal expression patterns of Dlx2 may be important in regulating the development of post-natal condyle in mice, and also offered a possible temporal‑mandibular joint osteoarthritis model animal for future studies.

No MeSH data available.


Related in: MedlinePlus

Expression of genes involved in condyle development in P90 Wnt1Cre::iZEG-Dlx2 mice. Immunofluorescence staining showed the expression level of the Dlx2 protein in the condylar region in (A) iZEG-Dlx2 and (B) P90 Wnt1Cre::iZEG-Dlx2 mice (Scale bar, 100 µm). OCN protein expression in the condylar region in (C) iZEG-Dlx2 and (D) P90 Wnt1Cre::iZEG-Dlx2 mice (Scale bar, 100 µm). Msx2 protein expression level in the condylar region of (E) iZEG-Dlx2 and (F) P90 Wnt1Cre::iZEG-Dlx2 mice (Scale bar, 50 µm). Dlx2, distal-less homeobox 2; OCN, osteocalcin; Msx, msh homeobox.
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f5-mmr-14-02-1624: Expression of genes involved in condyle development in P90 Wnt1Cre::iZEG-Dlx2 mice. Immunofluorescence staining showed the expression level of the Dlx2 protein in the condylar region in (A) iZEG-Dlx2 and (B) P90 Wnt1Cre::iZEG-Dlx2 mice (Scale bar, 100 µm). OCN protein expression in the condylar region in (C) iZEG-Dlx2 and (D) P90 Wnt1Cre::iZEG-Dlx2 mice (Scale bar, 100 µm). Msx2 protein expression level in the condylar region of (E) iZEG-Dlx2 and (F) P90 Wnt1Cre::iZEG-Dlx2 mice (Scale bar, 50 µm). Dlx2, distal-less homeobox 2; OCN, osteocalcin; Msx, msh homeobox.

Mentions: Immunofluorescence staining also indicated that Dlx2 expression levels were higher in the condylar region in P90 Wnt1Cre::iZEG-Dlx2 mice (Fig. 5A and B). The expression levels of OCN, a marker of osteogenesis, were downregulated in the condylar cartilage and bone region in P90 Wnt1Cre::iZEG-Dlx2 mice (Fig. 5C and D). Therefore, it is possible that osteogenesis has been impaired in the condylar region. The expression of Msx2, important for craniofacial bone development, which had been identified to interact with Dlx2 in previous studies (17–20), was upregulated in the condylar region, particularly in the resting layer and mineralized zone (Fig. 5E and F). Dlx2 may interact with Msx2 in the process of condyle development or degradation.


Overexpression of Dlx2 leads to postnatal condyle degradation.

Dai J, Si J, Zhu X, Zhang L, Wu D, Lu J, Ouyang N, Wang X, Shen G - Mol Med Rep (2016)

Expression of genes involved in condyle development in P90 Wnt1Cre::iZEG-Dlx2 mice. Immunofluorescence staining showed the expression level of the Dlx2 protein in the condylar region in (A) iZEG-Dlx2 and (B) P90 Wnt1Cre::iZEG-Dlx2 mice (Scale bar, 100 µm). OCN protein expression in the condylar region in (C) iZEG-Dlx2 and (D) P90 Wnt1Cre::iZEG-Dlx2 mice (Scale bar, 100 µm). Msx2 protein expression level in the condylar region of (E) iZEG-Dlx2 and (F) P90 Wnt1Cre::iZEG-Dlx2 mice (Scale bar, 50 µm). Dlx2, distal-less homeobox 2; OCN, osteocalcin; Msx, msh homeobox.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4940110&req=5

f5-mmr-14-02-1624: Expression of genes involved in condyle development in P90 Wnt1Cre::iZEG-Dlx2 mice. Immunofluorescence staining showed the expression level of the Dlx2 protein in the condylar region in (A) iZEG-Dlx2 and (B) P90 Wnt1Cre::iZEG-Dlx2 mice (Scale bar, 100 µm). OCN protein expression in the condylar region in (C) iZEG-Dlx2 and (D) P90 Wnt1Cre::iZEG-Dlx2 mice (Scale bar, 100 µm). Msx2 protein expression level in the condylar region of (E) iZEG-Dlx2 and (F) P90 Wnt1Cre::iZEG-Dlx2 mice (Scale bar, 50 µm). Dlx2, distal-less homeobox 2; OCN, osteocalcin; Msx, msh homeobox.
Mentions: Immunofluorescence staining also indicated that Dlx2 expression levels were higher in the condylar region in P90 Wnt1Cre::iZEG-Dlx2 mice (Fig. 5A and B). The expression levels of OCN, a marker of osteogenesis, were downregulated in the condylar cartilage and bone region in P90 Wnt1Cre::iZEG-Dlx2 mice (Fig. 5C and D). Therefore, it is possible that osteogenesis has been impaired in the condylar region. The expression of Msx2, important for craniofacial bone development, which had been identified to interact with Dlx2 in previous studies (17–20), was upregulated in the condylar region, particularly in the resting layer and mineralized zone (Fig. 5E and F). Dlx2 may interact with Msx2 in the process of condyle development or degradation.

Bottom Line: The model was constructed and the phenotype observed using gross observation, micro‑CT scan and histological examination.The model determined that overexpression of Dlx2 may lead to postnatal condyle malformation, subchondral bone degradation and irregular histological structure of the condylar cartilage.In addition, the expression of osteocalcin in the condyle region was markedly downregulated, whereas expression of msh homeobox 2 was upregulated.

View Article: PubMed Central - PubMed

Affiliation: Department of Oral and Cranio‑Maxillofacial Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai 200011, P.R. China.

ABSTRACT
Distal-less homeobox 2 (Dlx2), a member of the Dlx family of transcription factors, is important for the development of craniofacial tissues. Previous studies based on knock‑out mutant mice revealed that Dlx2 primarily disturbed the development of tissues from maxillary arch. The present study used a transgenic mouse model to specifically overexpress Dlx2 in neural crest cells in order to investigate the role of Dlx2 overexpression in post‑natal condyle in mice. The model was constructed and the phenotype observed using gross observation, micro‑CT scan and histological examination. The model determined that overexpression of Dlx2 may lead to postnatal condyle malformation, subchondral bone degradation and irregular histological structure of the condylar cartilage. In addition, the expression of osteocalcin in the condyle region was markedly downregulated, whereas expression of msh homeobox 2 was upregulated. The results of the present study suggest that Dlx2 overexpression in cranial neural crest cells would disrupt the development of post‑natal condyle, which demonstrates that the expression level and the spatiotemporal expression patterns of Dlx2 may be important in regulating the development of post-natal condyle in mice, and also offered a possible temporal‑mandibular joint osteoarthritis model animal for future studies.

No MeSH data available.


Related in: MedlinePlus