An update on transforming growth factor-β (TGF-β): Sources, types, functions and clinical applicability for cartilage/bone healing

Abstract

Transforming growth factor-β (TGF-β) has been reviewed for its sources, types of isoforms, biochemical effects on cartilage formation/repair, and its possible clinical applications. Purification of three isoforms (TGF-β-1, β-2 and β-3) and their biochemical characterization revealed mainly their homo-dimer nature, with heterodimers in traces, each monomer comprised of 112 amino acids and MW. of 12 500 Da. While histo-chemical staining by a variety of dyes has revealed precise localization of TGF-β in tissues, immune-blot technique has thrown light on their expression as a function of age (neonatal vs. adult), as also on its quantum in an active and latent state. X-ray crystallographic studies and nuclear magnetic resonance (NMR) analysis have unraveled mysteries of their three-dimensional structures, essential for understanding their functions. Their similarities have led to interchangeability in assays, while differences have led to their specialized clinical applicability. For this purpose, their latent (inactive) form is changed to an active form through enzymatic processes of phosphorylation/glycosylation/transamination/proteolytic degradation. Their functions encompass differentiation and de-differentiation of chondrocytes, synthesis of collagen and proteoglycans (PGs) and thereby maintain homeostasis of cartilage in several degenerative diseases and repair through cell cycle signaling and physiological control. While several factors affecting their performance are already identified, their interplay and chronology of sequences of functions is yet to be understood. For its success in clinical applications, challenges in judicious dealing with the factors and their interplay need to be understood.

Butein is a novel anti-adipogenic compound

“…SMAD3 represses MyoD function in myogenesis and inhibits CBAF1 during osteoblastic differentiation ( 44,45 ). TGF-␤ also promotes chondrogenesis and hematopoiesis ( 46 ). As TGF-␤ and its related proteins play an important role in regulating growth, development, and cell fate commitment of different cell types, it will be interesting to test the effects of butein in various cell types.…”

“…As TGF-␤ and its related proteins play an important role in regulating growth, development, and cell fate commitment of different cell types, it will be interesting to test the effects of butein in various cell types. TGF-␤ can also antagonize mitogenic actions of epithelial growth factor (EGF), fi broblast growth factor (FGF), and platelet derived growth factor (PDGF) ( 46 ). Similarly, a potent inhibitory effect of TGF-␤ in adipogenesis suggests that another molecular pathway might be modulated by TGF-␤ and SMAD signaling in preadipocytes.…”

Genetic expression of MMP-Matrix-mettalo-proteinases (MMP-1 and MMP-13) as a function of anterior mandibular repositioning appliance on the growth of mandibular condylar cartilage with and without administration of Insulin like growth factor (IGF-1) and Transforming growth factor-B (TGF-β)

“…1 Accordingly, besides growth factors, condylar growth modification is induced by mandibular advancement as reported by Petrovic and Stutzmann. 2 Most of the studies in this regard have used either histologic, histomorphometric, immuno-histomorphometric, biochemical or auto-radiographic methods as diagnostic tools to evaluate growth at the condyle [3][4][5][6][7] or to detect increased expression of some growth factors/ biomarkers of mandibular condylar cartilage (MCC) growth.…”

Proteomic Analysis of Gingival Tissue and Alveolar Bone during Alveolar Bone Healing

“…As expected, within the extracellular space, FN1 was coordinated with cellular assembly and organization and cellular maintenance, along with DCN, COL1A1, BGN, COL6A1, and POSTN. The possible link between these proteins is TGF-␤, which is crucial for connective tissue regeneration and bone remodeling (50,51). TGF-␤ affects osteoblast differentiation and bone formation (52,53) and increases transcription of osteoblast differentiation markers and alkaline phosphatase activity in murine bone marrow stromal cells (54).…”