Abstract
Cartilage homeostasis is governed by articular chondrocytes via their ability to modulate extracellular matrix production and degradation. In turn, chondrocyte activity is regulated by growth factors such as those of the transforming growth factor β (TGFβ) family. Members of this family include the TGFβs, bone morphogenetic proteins (BMPs), and growth and differentiation factors (GDFs). Signaling by this protein family uniquely activates SMAD-dependent signaling and transcription but also activates SMAD-independent signaling via MAPKs such as ERK and TAK1. This review will address the pivotal role of the TGFβ family in cartilage biology by listing several TGFβ family members and describing their signaling and importance for cartilage maintenance. In addition, it is discussed how (pathological) processes such as aging, mechanical stress, and inflammation contribute to altered TGFβ family signaling, leading to disturbed cartilage metabolism and disease.
Highlights
The transforming growth factor β (TGFβ) family of polypeptide growth factors controls development and homeostasis of many tissues, including articular cartilage
The only cell type present in this tissue is the chondrocyte, which is surrounded by a large amount of extracellular matrix (ECM) [1,3]
In pre-hypertrophic chondrocytes, SMAD1/5-RUNX2 interaction induces the activation of a reporter construct based on the Col10a1 promoter, the expression of which is an important phenotypic marker of hypertrophy [38,58]
Summary
The transforming growth factor β (TGFβ) family of polypeptide growth factors controls development and homeostasis of many tissues, including articular cartilage. The lamina splendens consists of collagen fibrils oriented in parallel to the the surface high levels hyaluronan andthe thelubricating lubricatingproteoglycan proteoglycanlubricin lubricin (PRG4),. The collagen are oriented isotropically cartilage surface [9], which efficient the tissueofupon compression to dissipate the to the cartilage surface [9],allows whichforallows forcollapse efficientofcollapse the tissue upon compression to energy of the the energy impact.ofThe this layer isofaccompanied by displacement and loss of water. The this layer is compacted, resistance further collapsetois further increased [1]. After formation of functional receptor complexes, TGFβ family members can activate multiple intracellular signaling pathways, which are categorized as either receptor SMAD (R-SMAD)-dependent or -independent, but R-SMAD-dependent signaling is regarded as the unique and canonical signaling pathway of TGFβ family members
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