Expressions of local renin-angiotensin system components in chondrocytes

Abstract

In 2013, we reported that local reninangiotensin system (local RAS) components express during the hypertrophic differentiation of chondrocytes and can modulate it, using ATDC5 cell line that involves differentiation from mesenchymal stem cells to calcified hypertrophic chondrocytes. However, the expressions of local RAS components in normal chondrocytes have not been revealed yet. The purpose of this study is to examine the expression of the local RAS components in chondrocytes in vivo and the conditions allowing the expression. We stained five major regions of 8-week-old C57BL/6 adult mice in which chondrocytes exist, including epiphyseal plates and hyaline cartilages, with antibodies to local RAS components. We also examined the expression of local RAS components in the cultured bovine’s articular cartilage chondrocytes using quantitative reverse transcription polymerase chain reaction and western blot analysis. In result, hypertrophic chondrocytes of epiphyseal plates included in the tibia and the lamina terminals expressed local RAS components. However, hyaline chondrocytes, including the knee articular cartilages, the parenchyma of nasal septums and of the tracheal walls, did not express local RAS components. Cultured bovine’s articular cartilage chondrocytes also did not express local RAS components. However, inducing hypertrophy by administering interleukin-1β or tumor necrosis factor-α, the cultured articular chondrocytes also expressed angiotensin II type 1 receptor and angiotensin II type 2 receptor. In conclusion, local RAS components express particularly in chondrocytes which occur hypertrophy and do not in hyaline chondrocytes. The results are in accord with our previous in vitro study. We think this novel knowledge is important to investigate cartilage hypertrophy and diseases induced by hypertrophic changes like osteoarthritis.

Chitotriosidase: A New Inflammatory Marker in Diabetic Complications

“…OA represents a major clinical and scientific challenge for clinicians and biologists due to the limited repair capacity of articular cartilage, which is rich in matrix proteins but also avascular [61]. Articular cartilage defects cause pain, reduced joint function, and significant disability [62].…”

Cyclic compressive loading activates angiotensin II type 1 receptor in articular chondrocytes and stimulates hypertrophic differentiation through a G‐protein‐dependent pathway

“…The angiotensin II (Ang II) type 1 receptor (AT1R) has been reported to be expressed in hypertrophic chondrocytes of human articular cartilage . In vitro , local RAS components are expressed in cultured chondrocytes and are involved in modulation of chondrocyte hypertrophic differentiation . Taken together, these findings suggest that the local RAS components in chondrocytes may be involved in cartilage degeneration through the hypertrophic differentiation of chondrocytes.…”

Continuous infusion of angiotensin II modulates hypertrophic differentiation and apoptosis of chondrocytes in cartilage formation in a fracture model mouse

“…On the other hand, it was already reported that Ang II induces inflammation and that Ang II activates, via AT1R, NF-κB 43,54,55 which regulates expression of various genes related to inflammation. Furthermore, inflammation by stimulation of IL-1β or tumor necrosis factor-α enhances the expressions of AT1R, 14 and inflammation by mechanical stress in OA activates AT1R. 50,51 Considering these findings, contribution of Ang II-induced inflammation to differentiation of chondrocytes is strongly suggested although it is still unclear how inflammation promotes differentiation of chondrocytes.…”

“…11 However, the effects of Ang II on chondrocytes and cartilage metabolism are still unclear, although Ang II receptors were shown to be expressed in cultured chondrocytes 12,13 and chondrocytes in vivo. 14 Some papers reported a beneficial effect of an angiotensin converting enzyme inhibitor (ACEI) or an Ang II receptor blocker (ARB) on fracture healing 15,16 in basic experiments, suggesting involvement of RAS in chondral metabolism. However, the direct effects of Ang II itself via Ang II receptors on differentiation, proliferation and apoptosis of chondrocytes, especially in vivo, are not yet fully understood.…”