Genetic studies and molecular cloning approaches have been successfully used to identify several transcription factors that regulate the numerous stages of cartilage development. Sex-determining region Y (SRY)-box 9 (Sox9) is an essential transcription factor for the initial stage of cartilage development. Sox5 and Sox6 play an important role in the chondrogenic action of Sox9, presumably by defining its cartilage specificity. Several transcription factors have been identified as transcriptional partners for Sox9 during cartilage development. Runt-related transcription factor 2 (Runx2) and Runx3 are necessary for hypertrophy of chondrocytes. CCAAT/enhancer-binding protein β (C/EBPβ) and activating transcription factor 4 (ATF4) function as co-activators for Runx2 during hypertrophy of chondrocytes. In addition, myocyte-enhancer factor 2C (Mef2C) is required for initiation of chondrocyte hypertrophy, presumably by functioning upstream of Runx2. Importantly, the pathogenic roles of several transcription factors in osteoarthritis have been demonstrated based on the similarity of pathological phenomena seen in osteoarthritis with chondrocyte hypertrophy. We discuss the importance of investigating cellular and molecular properties of articular chondrocytes and degradation mechanisms in osteoarthritis, one of the most common cartilage diseases.
Activating Transcription Factor 4 ; Cartilage Diseases ; Cartilage* ; Chondrocytes ; Cloning, Molecular ; Hypertrophy ; Osteoarthritis ; Sensitivity and Specificity ; Transcription Factors*

Endochondral ossification is the fundamental process of skeletal development in vertebrates. Chondrocytes undergo sequential steps of differentiation, including mesenchymal condensation, proliferation, hypertrophy, and mineralization. These steps, which are required for the morphological and functional changes in differentiating chondrocytes, are strictly regulated by a complex transcriptional network. Biochemical and mice genetic studies identified chondrogenic transcription factors critical for endochondral ossification. The transcription factor sex-determining region Y (SRY)-box 9 (Sox9) is essential for early chondrogenesis, and impaired Sox9 function causes severe chondrodysplasia in humans and mice. In addition, recent genome-wide chromatin immunoprecipitation-sequencing studies revealed the precise regulatory mechanism of Sox9 during early chondrogenesis. Runt-related transcription factor 2 promotes chondrocyte hypertrophy and terminal differentiation. Interestingly, endoplasmic reticulum (ER) stress-related transcription factors have recently emerged as novel regulators of chondrocyte differentiation. Here we review the transcriptional mechanisms that regulate endochondral ossification, with a focus on Sox9.
Animals ; Chondrocytes ; Chondrogenesis ; Chromatin ; Endoplasmic Reticulum ; Gene Regulatory Networks* ; Humans ; Hypertrophy ; Mice ; Miners ; Osteogenesis ; SOX9 Transcription Factor ; Transcription Factors ; Vertebrates

A 53-year-old woman with rheumatoid arthritis had been suffering from right thumb deformity for a couple of months. Due to this, she was unable to perform the pinch movement. There were surgical options to treat the deformity, but the patient declined surgery. We therefore surmised whether we could correct the deformity with a splint. In 2012, we then proposed the use of a finger splint. The patient's finger function improved, and as of 2021, she was still using the finger splint without any problems. Thus, it is recommended to use a finger splint for thumb deformity because it is easier and less invasive than surgery.

A 53-year-old woman with rheumatoid arthritis had been suffering from right thumb deformity for a couple of months. Due to this, she was unable to perform the pinch movement. There were surgical options to treat the deformity, but the patient declined surgery. We therefore surmised whether we could correct the deformity with a splint. In 2012, we then proposed the use of a finger splint. The patient's finger function improved, and as of 2021, she was still using the finger splint without any problems. Thus, it is recommended to use a finger splint for thumb deformity because it is easier and less invasive than surgery.