Article

Osterix Regulates Calcification and Degradation of Chondrogenic Matrices through Matrix Metalloproteinase 13 (MMP13) Expression in Association with Transcription Factor Runx2 during Endochondral Ossification.

From the Department of Molecular and Cellular Biochemistry, Osaka University Graduate School of Dentistry, 1-8 Yamadaoka, Suita, Osaka 565-0871, Japan.
Journal of Biological Chemistry (Impact Factor: 4.65). 08/2012; 287(40):33179-90. DOI: 10.1074/jbc.M111.337063
Source: PubMed

ABSTRACT Endochondral ossification is temporally and spatially regulated by several critical transcription factors, including Sox9, Runx2, and Runx3. Although the molecular mechanisms that control the late stages of endochondral ossification (e.g. calcification) are physiologically and pathologically important, these precise regulatory mechanisms remain unclear. Here, we demonstrate that Osterix is an essential transcription factor for endochondral ossification that functions downstream of Runx2. The global and conditional Osterix-deficient mice studied here exhibited a defect of cartilage-matrix ossification and matrix vesicle formation. Importantly, Osterix deficiencies caused the arrest of endochondral ossification at the hypertrophic stage. Microarray analysis revealed that matrix metallopeptidase 13 (MMP13) is an important target of Osterix. We also showed that there exists a physical interaction between Osterix and Runx2 and that these proteins function cooperatively to induce MMP13 during chondrocyte differentiation. Most interestingly, the introduction of MMP13 stimulated the calcification of matrices in Osterix-deficient mouse limb bud cells. Our results demonstrated that Osterix was essential to endochondral ossification and revealed that the physical and functional interaction between Osterix and Runx2 were necessary for the induction of MMP13 during endochondral ossification.

0 Bookmarks
 · 
100 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: The effect of unilateral anterior crossbite on the remodelling of mandibular condyle needs to be investigated. This study aimed to investigate the effects of experimentally created unilateral anterior crossbite on the remodelling of mandibular condyle and explore the changes in the expression of relevant transcription factors and growth factors. The experimental unilateral anterior crossbite was created in 6-week-old female growing rats by bonding metal tubes to the left pairs of incisors. Remodelings of mandibular condylar cartilage was assessed histologically at 2, 4 and 8 weeks. Protein and mRNA levels of Sox9, runt-related transcription factor 2 (Runx2), Osterix (Osx), transforming growth factor beta 1 (TGFβ1), transforming growth factor beta receptor 2 (TGFβr2) and type X collagen (ColX) were investigated by immunohistochemistry and real-time PCR, while alkaline phosphatise (ALP) by histochemistry and real-time PCR. Decreased ratio of hypertrophic cartilage layer was noticed in the 4w experimental group versus controls. At all the time points, the expression of Sox9 and ALP increased but that of TGFβ1 and TGFβr2 decreased in experimental groups (P < 0·05). The expression of Runx2, Osx and Col X increased at 2w, but decrease at 4w (P < 0·05). The results that obvious cartilage degradation and altered expression of related transcription factors and growth factors were detected in the mandibular condyles of the experimental group suggested that the present unilateral anterior crossbite plays an adverse role in the TMJ, and thus leading to the degenerative endochondral ossification.
    Journal of Oral Rehabilitation 05/2013; · 2.34 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Deer antlers are the only mammalian appendages to display an annual cycle of full regeneration. However, little is known about the molecular mechanisms of antler regeneration. Our previous study has demonstrated that parathyroid hormone-related peptide (PTHrP) can promote proliferation of antler chondrocytes and inhibit its differentiation, but the mechanism underlying such regulation is not fully understood. We have determined the role of PTHrP on the mRNA expression of matrix metalloproteinase-9 (MMP9) and MMP13 in the antler chondrocytes. The possible pathways that transduce PTHrP effects were examined. In situ hybridization showed that MMP9 and MMP13 were mainly localized in the dermal fibroblasts, perichondrium and cartilage in the sika deer antler, of which MMP9 and MMP13 were highly expressed in the chondrocytes. Exogenous PTHrP could inhibit the expression of MMP9 and MMP13 in the antler chondrocytes. The inhibitory effect of PTHrP on MMP9 was abolished by JNK inhibitor, SP600125, while P38MAPK inhibitor SB203850 and PKC inhibitor GF109203X could rescue the inhibitory effect of PTHrP on MMP13. The results suggest that PTHrP can inhibit MMP9 expression by JNK signaling pathway and MMP13 expression by p38MAPK and PKC signaling pathways in the antler chondrocytes.Thus PTHrP is involved in the control of antler chondrocytes maturation and cartilage matrix degradation.
    Cell Biology International 08/2013; · 1.64 Impact Factor
  • Source
    Heart 08/1956; 18(3):320-6.