The Signaling Pathways Involved in Chondrocyte Differentiation and Hypertrophic Differentiation

Abstract

Chondrocytes communicate with each other mainly via diffusible signals rather than direct cell-to-cell contact. The chondrogenic differentiation of mesenchymal stem cells (MSCs) is well regulated by the interactions of varieties of growth factors, cytokines, and signaling molecules. A number of critical signaling molecules have been identified to regulate the differentiation of chondrocyte from mesenchymal progenitor cells to their terminal maturation of hypertrophic chondrocytes, including bone morphogenetic proteins (BMPs), SRY-related high-mobility group-box gene 9 (Sox9), parathyroid hormone-related peptide (PTHrP), Indian hedgehog (Ihh), fibroblast growth factor receptor 3 (FGFR3), and β-catenin. Except for these molecules, other factors such as adenosine, O2 tension, and reactive oxygen species (ROS) also have a vital role in cartilage formation and chondrocyte maturation. Here, we outlined the complex transcriptional network and the function of key factors in this network that determine and regulate the genetic program of chondrogenesis and chondrocyte differentiation.

Perfusion Enhances Hypertrophic Chondrocyte Matrix Deposition, But Not the Bone Formation

“…The progression of in vivo endochondral ossification is thought to be controlled by a number of cytokines, with BMPs, IHH/PTHrP, and Wnt/beta-catenin, providing key pathways to regulate bone formation. [49][50][51] In previous studies, cytokines produced by differentiated hypertrophic chondrocytes influenced bone formation and remodeling. 52 In this study, the flow rate did not affect the BMP concentration, indicating that the BMP pathways activated by the tissue-engineered grafts upon implantation did not play a significant role in bone regeneration.…”

Stress‐Induced Evolutionary Innovation: A Mechanism for the Origin of Cell Types

“…The study of all these phenomena constitutes the field of cellular stress biology, which has been separated from “normal” developmental biology and physiology for decades. Increasingly, however, the boundary between these fields is blurred because mechanisms and agents common to the field of stress biology, such as apoptosis or ROS, have been found to play a role in “normal” biological processes like cell differentiation . This overlap between stress biology and developmental biology is not coincidental.…”

Matrix remodeling and mechanotransduction in in vitro chondrogenesis: Implications towards functional stem cell‐based cartilage tissue engineering

“…SOX9 binds to the promoter region of the collagen type II gene and results in the expression of the said gene. It is reported that in the absence of SOX9, the chondrogenesis is blocked at the initial stages of mesenchymal condensation and hence forms a critical marker . The nondifferentiated state of stem cells, as well as fibrocartilage initiation, is evaluated by the expression of collagen type 1 gene .…”