Role of Runx genes in chondrocyte differentiation

Runx2/Cbfa1 plays a central role in skeletal development as demonstrated by the absence of osteoblasts/bone in mice with inactivated Runx2/Cbfa1 alleles. To further investigate the role of Runx2 in cartilage differentiation and to assess the potential of Runx2 to induce bone formation, we cloned chicken Runx2 and overexpressed it in chick embryos using a retroviral system. Infected chick wings showed multiple phenotypes consisting of (1) joint fusions, (2) expansion of carpal elements, and (3) shortening of skeletal elements. In contrast, bone formation was not affected. To investigate the function of Runx2/Cbfa1 during cartilage development, we have generated transgenic mice that express a dominant negative form of Runx2 in cartilage. The selective inactivation of Runx2 in chondrocytes results in a severe shortening of the limbs due to a disturbance in chondrocyte differentiation, vascular invasion, osteoclast differentiation, and periosteal bone formation. Analysis of the growth plates in transgenic mice and in chick limbs shows that Runx2 is a positive regulator of chondrocyte differentiation and vascular invasion. The results further indicate that Runx2 promotes chondrogenesis either by maintaining or by initiating early chondrocyte differentiation. Furthermore, Runx2 is essential but not sufficient to induce osteoblast differentiation. To analyze the role of runx genes in skeletal development, we performed in situ hybridization with Runx2- and Runx3-specific probes. Both genes were coexpressed in cartilaginous condensations, indicating a cooperative role in the regulation of early chondrocyte differentiation and thus explaining the expansion/maintenance of cartilage in the carpus and joints of infected chick limbs.     

Pathological mechanism of chondrocytes and the surrounding environment during osteoarthritis of temporomandibular joint

Temporomandibular joint (TMJ) osteoarthritis is a common chronic degenerative disease of the TMJ. In order to explore its aetiology and pathological mechanism, many animal models and cell models have been constructed to simulate the pathological process of TMJ osteoarthritis. The main pathological features of TMJ osteoarthritis include chondrocyte death, extracellular matrix (ECM) degradation and subchondral bone remodelling. Chondrocyte apoptosis accelerates the destruction of cartilage. However, autophagy has a protective effect on condylar chondrocytes. Degradation of ECM not only changes the properties of cartilage but also affects the phenotype of chondrocytes. The loss of subchondral bone in the early stages of TMJ osteoarthritis plays an aetiological role in the onset of osteoarthritis. In recent years, increasing evidence has suggested that chondrocyte hypertrophy and endochondral angiogenesis promote TMJ osteoarthritis. Hypertrophic chondrocytes secrete many factors that promote cartilage degeneration. These chondrocytes can further differentiate into osteoblasts and osteocytes and accelerate cartilage ossification. Intrachondral angiogenesis and neoneurogenesis are considered to be important triggers of arthralgia in TMJ osteoarthritis. Many molecular signalling pathways in endochondral osteogenesis are responsible for TMJ osteoarthritis. These latest discoveries in TMJ osteoarthritis have further enhanced the understanding of this disease and contributed to the development of molecular therapies. This paper summarizes recent cognition on the pathogenesis of TMJ osteoarthritis, focusing on the role of chondrocyte hypertrophy degeneration and cartilage angiogenesis.     

Load application induces changes in the expression levels of Sox-9, FGFR-3 and VEGF in condylar chondrocytes

Experimental and clinical observations have proven the modulatory effects of mechanical loading on the development and maintenance of cartilage architecture. Here we examined the involvement of Sox-9, FGFR-3 and VEGF (pivotal factors controlling cartilage development and growth) in the mechano-transduction pathway of mandibular condylar cartilage by changing the dynamics of the transmitted load via changes in food hardness. To this end, condyle cartilage tissue of rats fed with hard or soft food was analyzed immunohistochemically at various time points. Our findings demonstrate that different mechanical loading conditions in condylar chondrocytes trigger differentiation-/maturation-related processes by affecting the expression levels of these factors, ultimately influencing condylar cartilage growth.     

成骨细胞特异性转录因子2与乳腺癌

Runx2为成骨细胞特异性转录因子,调控成骨细胞分化和骨组织的形成.近年来研究表明,Runx2在乳腺癌中可以激活与癌症转移相关的骨基质、黏附蛋白、金属蛋白酶以及血管内皮生长因子,并且Runx2可以与一些联合抑制剂或激活剂形成调控复合体,在亚核结构域中存在,调节基因的转录以及间接地影响乳腺癌细胞的信号通路.除此之外,Runx2还可以与雌激素受体相互作用在某种程度上解除雌激素及其受体在乳腺癌发展中的调控作用.本文主要概括Runx2在乳腺癌中的作用机制,重点综述Runx2在乳腺癌中与雌激素受体相互作用的研究进展.