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Transforming growth factor Beta family: insight into the role of growth factors in regulation of fracture healing biology and potential clinical applications.

Poniatowski ŁA, Wojdasiewicz P, Gasik R, Szukiewicz D - Mediators Inflamm. (2015)

Bottom Line: Pleiotropic and redundant functions of the TGF-β family concern control of numerous aspects and effects of cell functions, including proliferation, differentiation, and migration, in all tissues of the human body.Numerous in vivo and in vitro studies in various models analysing cytokines and growth factors' involvement have shown that TGF-β has a leading role in the fracture healing process.This paper sums up current knowledge on the basis of available literature concerning the role of the TGF-β family in the fracture healing process.

View Article: PubMed Central - PubMed

Affiliation: Department of General and Experimental Pathology with Centre for Preclinical Research and Technology (CePT), Second Faculty of Medicine, Medical University of Warsaw, Pawińskiego 3c, 02-106 Warsaw, Poland.

ABSTRACT
The transforming growth factor beta (TGF-╬▓) family forms a group of three isoforms, TGF-╬▓1, TGF-╬▓2, and TGF-╬▓3, with their structure formed by interrelated dimeric polypeptide chains. Pleiotropic and redundant functions of the TGF-╬▓ family concern control of numerous aspects and effects of cell functions, including proliferation, differentiation, and migration, in all tissues of the human body. Amongst many cytokines and growth factors, the TGF-╬▓ family is considered a group playing one of numerous key roles in control of physiological phenomena concerning maintenance of metabolic homeostasis in the bone tissue. By breaking the continuity of bone tissue, a spread-over-time and complex bone healing process is initiated, considered a recapitulation of embryonic intracartilaginous ossification. This process is a cascade of local and systemic phenomena spread over time, involving whole cell lineages and various cytokines and growth factors. Numerous in vivo and in vitro studies in various models analysing cytokines and growth factors' involvement have shown that TGF-╬▓ has a leading role in the fracture healing process. This paper sums up current knowledge on the basis of available literature concerning the role of the TGF-╬▓ family in the fracture healing process.

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Related in: MedlinePlus

A schematic representation of TGF-╬▓ superfamily. TGF-╬▓: transforming growth factor beta; GDF: growth and differentiation factor; ACT: activin; INH: inhibin; other ligands include M├╝llerian inhibiting substance (MIS) or anti-M├╝llerian hormone (AMH), left-right determination factor (Lefty), and nodal growth differentiation factor (Nodal); GDNF: glial-derived neurotrophic factors; BMPs: bone morphogenetic proteins.
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fig1: A schematic representation of TGF-╬▓ superfamily. TGF-╬▓: transforming growth factor beta; GDF: growth and differentiation factor; ACT: activin; INH: inhibin; other ligands include M├╝llerian inhibiting substance (MIS) or anti-M├╝llerian hormone (AMH), left-right determination factor (Lefty), and nodal growth differentiation factor (Nodal); GDNF: glial-derived neurotrophic factors; BMPs: bone morphogenetic proteins.

Mentions: Disorders involving the musculoskeletal system are one of the most diversified groups of diseases [1]. They include congenital and acquired diseases directly affecting bones, joints, ligaments, and muscles, as well as disorders, in which this system is involved secondarily [2]. All musculoskeletal system disorders represent a continuous challenge to the society, considering their complex and often multifactor aetiology, varied course, and economic aspects, as well as a still present problem of implementing optimal surgical and nonsurgical treatment [1, 2]. One of the most serious conditions encountered in the clinical practice is fractures, that is, breaking of the bone continuity caused by an injury or other reasons, including osteoporosis, cancer, or other systemic diseases [2, 3]. The bone damage can also be accompanied by soft tissues damage of different extent, also affecting crucial structures such as vessels and nerves [4]. Any tissue damage, caused by the injury or the surgery itself, involves not only a local immunological response and inflammation, but also a systemic immunological response related to inflow, migration, and proliferation of a broad spectrum of cells [5ÔÇô9]. Cytokines are molecules responsible for controlling intracellular communication and directing the immunological reaction [10]. This group of low-molecular glycoproteins forms a ÔÇťcytokine networkÔÇŁ in the body [11, 12]. Amongst cytokines identified and described so far, a group of growth factors (GF) can also be distinguished, whose effects in certain situations can also be viewed in a context of a ÔÇťgrowth factor networkÔÇŁ [13]. The transforming growth factor beta (TGF-╬▓) superfamily requires a particular attention. The TGF-╬▓ superfamily is a large and continuously expanded group of regulatory polypeptides, including a model transforming growth factor beta family and other families, such as bone morphogenetic proteins (BMPs), growth and differentiation factors (GDFs), activins (ACTs), inhibins (INHs), and glial-derived neurotrophic factors (GDNFs), as well as some proteins not included in the above families, such as M├╝llerian inhibiting substance (MIS), also known as anti-M├╝llerian hormone (AMH), left-right determination factor (Lefty), and nodal growth differentiation factor (Nodal) [14] (Figure 1).


Transforming growth factor Beta family: insight into the role of growth factors in regulation of fracture healing biology and potential clinical applications.

Poniatowski ŁA, Wojdasiewicz P, Gasik R, Szukiewicz D - Mediators Inflamm. (2015)

A schematic representation of TGF-╬▓ superfamily. TGF-╬▓: transforming growth factor beta; GDF: growth and differentiation factor; ACT: activin; INH: inhibin; other ligands include M├╝llerian inhibiting substance (MIS) or anti-M├╝llerian hormone (AMH), left-right determination factor (Lefty), and nodal growth differentiation factor (Nodal); GDNF: glial-derived neurotrophic factors; BMPs: bone morphogenetic proteins.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4325469&req=5

fig1: A schematic representation of TGF-╬▓ superfamily. TGF-╬▓: transforming growth factor beta; GDF: growth and differentiation factor; ACT: activin; INH: inhibin; other ligands include M├╝llerian inhibiting substance (MIS) or anti-M├╝llerian hormone (AMH), left-right determination factor (Lefty), and nodal growth differentiation factor (Nodal); GDNF: glial-derived neurotrophic factors; BMPs: bone morphogenetic proteins.
Mentions: Disorders involving the musculoskeletal system are one of the most diversified groups of diseases [1]. They include congenital and acquired diseases directly affecting bones, joints, ligaments, and muscles, as well as disorders, in which this system is involved secondarily [2]. All musculoskeletal system disorders represent a continuous challenge to the society, considering their complex and often multifactor aetiology, varied course, and economic aspects, as well as a still present problem of implementing optimal surgical and nonsurgical treatment [1, 2]. One of the most serious conditions encountered in the clinical practice is fractures, that is, breaking of the bone continuity caused by an injury or other reasons, including osteoporosis, cancer, or other systemic diseases [2, 3]. The bone damage can also be accompanied by soft tissues damage of different extent, also affecting crucial structures such as vessels and nerves [4]. Any tissue damage, caused by the injury or the surgery itself, involves not only a local immunological response and inflammation, but also a systemic immunological response related to inflow, migration, and proliferation of a broad spectrum of cells [5ÔÇô9]. Cytokines are molecules responsible for controlling intracellular communication and directing the immunological reaction [10]. This group of low-molecular glycoproteins forms a ÔÇťcytokine networkÔÇŁ in the body [11, 12]. Amongst cytokines identified and described so far, a group of growth factors (GF) can also be distinguished, whose effects in certain situations can also be viewed in a context of a ÔÇťgrowth factor networkÔÇŁ [13]. The transforming growth factor beta (TGF-╬▓) superfamily requires a particular attention. The TGF-╬▓ superfamily is a large and continuously expanded group of regulatory polypeptides, including a model transforming growth factor beta family and other families, such as bone morphogenetic proteins (BMPs), growth and differentiation factors (GDFs), activins (ACTs), inhibins (INHs), and glial-derived neurotrophic factors (GDNFs), as well as some proteins not included in the above families, such as M├╝llerian inhibiting substance (MIS), also known as anti-M├╝llerian hormone (AMH), left-right determination factor (Lefty), and nodal growth differentiation factor (Nodal) [14] (Figure 1).

Bottom Line: Pleiotropic and redundant functions of the TGF-β family concern control of numerous aspects and effects of cell functions, including proliferation, differentiation, and migration, in all tissues of the human body.Numerous in vivo and in vitro studies in various models analysing cytokines and growth factors' involvement have shown that TGF-β has a leading role in the fracture healing process.This paper sums up current knowledge on the basis of available literature concerning the role of the TGF-β family in the fracture healing process.

View Article: PubMed Central - PubMed

Affiliation: Department of General and Experimental Pathology with Centre for Preclinical Research and Technology (CePT), Second Faculty of Medicine, Medical University of Warsaw, Pawińskiego 3c, 02-106 Warsaw, Poland.

ABSTRACT
The transforming growth factor beta (TGF-╬▓) family forms a group of three isoforms, TGF-╬▓1, TGF-╬▓2, and TGF-╬▓3, with their structure formed by interrelated dimeric polypeptide chains. Pleiotropic and redundant functions of the TGF-╬▓ family concern control of numerous aspects and effects of cell functions, including proliferation, differentiation, and migration, in all tissues of the human body. Amongst many cytokines and growth factors, the TGF-╬▓ family is considered a group playing one of numerous key roles in control of physiological phenomena concerning maintenance of metabolic homeostasis in the bone tissue. By breaking the continuity of bone tissue, a spread-over-time and complex bone healing process is initiated, considered a recapitulation of embryonic intracartilaginous ossification. This process is a cascade of local and systemic phenomena spread over time, involving whole cell lineages and various cytokines and growth factors. Numerous in vivo and in vitro studies in various models analysing cytokines and growth factors' involvement have shown that TGF-╬▓ has a leading role in the fracture healing process. This paper sums up current knowledge on the basis of available literature concerning the role of the TGF-╬▓ family in the fracture healing process.

Show MeSH
Related in: MedlinePlus