Impact of Fluid Flow Shear Stress on Osteoblast Differentiation and Cross-Talk with Articular Chondrocytes

Abstract

Bone cells, in particular osteoblasts, are capable of communication with each other during bone growth and homeostasis. More recently it has become clear that they also communicate with other cell-types; including chondrocytes in articular cartilage. One way that this process is facilitated is by interstitial fluid movement within the pericellular and extracellular matrices. This stimulus is also an important mechanical signal in skeletal tissues, and is known to generate shear stresses at the micron-scale (known as fluid flow shear stresses (FFSS)). The primary aim of this study was to develop and characterize an in vitro bone–cartilage crosstalk system, to examine the effect of FFSS on these cell types. Specifically, we evaluated the response of osteoblasts and chondrocytes to FFSS and the effect of FFSS-induced soluble factors from the former, on the latter. This system will ultimately be used to help us understand the role of subchondral bone damage in articular cartilage degeneration. We also carried out a comparison of responses between cell lines and primary murine cells in this work. Our findings demonstrate that primary cells produce a more reliable and reproducible response to FFSS. Furthermore we found that at lower magnitudes , direct FFSS produces anabolic responses in both chondrocytes and osteoblasts, whereas higher levels produce more catabolic responses. Finally we show that exposure to osteoblast-derived factors in conditioned media experiments produced similarly catabolic changes in primary chondrocytes.

Fluid Shear Stress Regulates Osteogenic Differentiation via AnnexinA6-Mediated Autophagy in MC3T3-E1 Cells

“…However, FSS-induced osteogenic differentiation is not always of FSS magnitude or duration-dependent. Higher stresses or a long duration may lead to damaging or negative responses, which was also reported in previous studies [ 32 ]. Accordingly, the proper magnitude and duration of FSS are vital for osteogenesis.…”

Identification of osteoblastic autophagy-related genes for predicting diagnostic markers in osteoarthritis

“… 71 , 72 Additionally, under the influence of high fluid flow shear stress levels, the soluble factors secreted by osteoblasts lead to a reduction in the synthetic metabolism and an enhancement in the catabolic metabolism of chondrocytes. 73 Our results also suggest that the secretion of osteogenic factors may be the key to regulating cartilage metabolism. In vitro co-culture experiments have provided insights into the molecular and cellular interactions between chondrocytes and osteoblasts.…”

METTL3-mediated m6A modification increases Hspa1a stability to inhibit osteoblast aging

“…Firstly, the role of METTL3 in osteoblast function was explored by stimulating osteoblast activity. Certain factors, such as hormones [ 25 , 26 ], growth factors [ 27 , 28 ], and fluid shear stress (FSS) [ 29 , 30 ], have been shown to positively stimulate osteoblast activity. Drawing from previous studies [ 31 , 32 ] and our preliminary findings, FSS has been confirmed to promote the physiological function of osteoblasts, leading to increased bone formation and reduced risk of the developing osteoporosis [ 33 – 36 ].…”