The aim of this study was to investigate the temporal expression of TIMP-1 within endochondral and intramembranous bone grafts during the early stages of healing in thirty six adult New Zealand white rabbits. Total RNA was isolated from bone grafts extracted on days 0-11 and day 14 post-grafting, for RT-PCR analysis. In situ hybridization was carried out on days 1-9 and day 14. Results showed T...

Runx2 and Axin2 regulate skeletal development. We recently determined that Axin2 and Runx2 molecularly interact in differentiating osteoblasts to regulate intramembranous bone formation, but the relationship between these factors in endochondral bone formation was unresolved. To address this, we examined the effects of Axin2 deficiency on the cleidocranial dysplasia (CCD) phenotype of Runx2(+/-...

Chondrocyte hypertrophy is essential for endochondral bone development. Unexpectedly, we discovered that MEF2C, a transcription factor that regulates muscle and cardiovascular development, controls bone development by activating the gene program for chondrocyte hypertrophy. Genetic deletion of Mef2c or expression of a dominant-negative MEF2C mutant in endochondral cartilage impairs hypertrophy,...

INTRODUCTION The mammalian skull vault, which protects the brain, comprises bones derived from dual embryonic origins. Cells from both cranial neural crest (CNC) and paraxial mesoderm (PM) form skull progenitors, and these distinct populations are already spatially segregated in rostral and caudal domains above the eye in the mouse at E11.5 (Yoshida et al., 2008). Skull bones undergo intramembr...

In brief: Chondrocyte-specific ablation of the mechano-sensory Piezo1 results in substantially impaired formation secondary spongiosa during endochondral bone formation. The study explores this unexpected finding and show that mechano-sensing growth plate chondrocytes directly regulates trabeculae spongiosa.

According to current dogma, chondrocytes and osteoblasts are considered independent lineages derived from a common osteochondroprogenitor. In endochondral bone formation, chondrocytes undergo a series of differentiation steps to form the growth plate, and it generally is accepted that death is the ultimate fate of terminally differentiated hypertrophic chondrocytes (HCs). Osteoblasts, accompany...

During endochondral bone development, the first osteoblasts differentiate in the perichondrium surrounding avascular cartilaginous rudiments; the source of trabecular osteoblasts inside the later bone is, however, unknown. Here, we generated tamoxifen-inducible transgenic mice bred to Rosa26R-LacZ reporter mice to follow the fates of stage-selective subsets of osteoblast lineage cells. Pulse-ch...

Transforming growth factor beta (TGF-β) is a multifunctional protein that induces gene expression of cartilage-specific molecules, but its exact role in the process of chondrogenesis is unclear. Because recent studies suggest that TGF-β can facilitate chondrogenic precursor cells differentiating into chondrocytes, we sought to determine whether TGF-β prevents denervation-induced reduction of en...

We previously reported that transcription factor XBP1S binds to RUNX2 and enhances chondrocyte hypertrophy through acting as a cofactor of RUNX2. Herein, we report that XBP1S is a key downstream molecule of BMP2 and is required for BMP2-mediated chondrocyte differentiation. XBP1S is up-regulated during chondrocyte differentiation and demonstrates the temporal and spatial expression pattern duri...

Skeletogenesis and bone fracture healing involve endochondral ossification, a process during which cartilaginous primordia are gradually replaced by bone tissue. In line with a role for cyclooxygenase-2 (COX-2) in the endochondral ossification process, non-steroidal anti-inflammatory drugs (NSAIDs) were reported to negatively affect bone fracture healing due to impaired osteogenesis. However, a...