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Concerted stimuli regulating osteo-chondral differentiation from stem cells: phenotype acquisition regulated by microRNAs.

Gordeladze JO, Djouad F, Brondello JM, Noël D, Duroux-Richard I, Apparailly F, Jorgensen C - Acta Pharmacol. Sin. (2009)

Bottom Line: These act on stem cells (SCs) recruited for lineage-specific differentiation, with cellular phenotypes representing various functions throughout their life span.The signals are rendered by hormones and growth factors (GFs) and mechanical forces ensuring proper modelling and remodelling of bone and cartilage, due to indigenous and programmed metabolism in SCs, osteoblasts, chondrocytes, as well as osteoclasts and other cell types (eg T helper cells).This review focuses on the concerted action of such signals, as well as the regulatory and/or stabilizing control circuits rendered by a class of small RNAs, designated microRNAs.The present approach to cell differentiation in vitro may vastly influence cell engineering for in vivo tissue repair.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, Institute for Basal Medical Sciences, Medical Faculty, University of Oslo, Norway. j.o.gordeladze@medisin.uio.no

ABSTRACT
Bone and cartilage are being generated de novo through concerted actions of a plethora of signals. These act on stem cells (SCs) recruited for lineage-specific differentiation, with cellular phenotypes representing various functions throughout their life span. The signals are rendered by hormones and growth factors (GFs) and mechanical forces ensuring proper modelling and remodelling of bone and cartilage, due to indigenous and programmed metabolism in SCs, osteoblasts, chondrocytes, as well as osteoclasts and other cell types (eg T helper cells).This review focuses on the concerted action of such signals, as well as the regulatory and/or stabilizing control circuits rendered by a class of small RNAs, designated microRNAs. The impact on cell functions evoked by transcription factors (TFs) via various signalling molecules, also encompassing mechanical stimulation, will be discussed featuring microRNAs as important members of an integrative system. The present approach to cell differentiation in vitro may vastly influence cell engineering for in vivo tissue repair.

Show MeSH
The differentiation of stem cells (SCs) towards osteoblasts. The impact of hormones and growth factors (GFs), mechanical loading, as well as transcription factors (TFs) and TF-modulating proteins are indicated. Some TFs and TF-modulating proteins are negatively or positively influencing the activity of Runx2, while others are involved in the differentiation process independently of Runx2. MicroRNA species negatively affecting the differentiation of SCs elicited by GFs and/or TFs are depicted (see especially microRNAs 29, 125, 133, and 135). The osteoblast secretes matrix proteins, whose gene transcripts are modulated by TFs. It also affects osteoclast differentiation and activation by secreting the opposite acting factors RANK-L and OPG. Finally, the osteoblast might be subjected to apoptosis or acquiring an osteocytic state. Osteocytes serve as a connection between the bone tissue and the nervous system, while also perceiving the mechanical load on the skeleton.
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fig1: The differentiation of stem cells (SCs) towards osteoblasts. The impact of hormones and growth factors (GFs), mechanical loading, as well as transcription factors (TFs) and TF-modulating proteins are indicated. Some TFs and TF-modulating proteins are negatively or positively influencing the activity of Runx2, while others are involved in the differentiation process independently of Runx2. MicroRNA species negatively affecting the differentiation of SCs elicited by GFs and/or TFs are depicted (see especially microRNAs 29, 125, 133, and 135). The osteoblast secretes matrix proteins, whose gene transcripts are modulated by TFs. It also affects osteoclast differentiation and activation by secreting the opposite acting factors RANK-L and OPG. Finally, the osteoblast might be subjected to apoptosis or acquiring an osteocytic state. Osteocytes serve as a connection between the bone tissue and the nervous system, while also perceiving the mechanical load on the skeleton.

Mentions: The differentiation of MSCs towards osteoblasts undergoes several phases including osteoprogenitor cells, their differentiation into pre-osteoblasts and mature osteoblasts. The latter are transformed into osteocytes, which may constitute the mechano-sensing lattice and nervous system junction connecting bone to the outer “environment”2, 5, 34, 35, 36, 37, 38, 39, 40, or they are subjected to apoptosis (Figure 1). A concerted action of both positive and negative regulatory factors determines the developing phenotype of the osteoblastic cells, including the processes of bone modelling and remodelling. This involves the concerted action of secreted RANK-L and OPG, acting on osteoclastic cells2, 4, 5, 6, 41, 42. Major functional features of the osteoblast pertain to sequential synthesis and deposition of matrix proteins and enzymes necessary to complete these processes. Finally, the transition of osteoblasts to osteocytes are also modulated by several factors (Figure 1), yielding a complete and versatile cellular system, being able to adapt to various physiological conditions, when necessary2, 5, 43.


Concerted stimuli regulating osteo-chondral differentiation from stem cells: phenotype acquisition regulated by microRNAs.

Gordeladze JO, Djouad F, Brondello JM, Noël D, Duroux-Richard I, Apparailly F, Jorgensen C - Acta Pharmacol. Sin. (2009)

The differentiation of stem cells (SCs) towards osteoblasts. The impact of hormones and growth factors (GFs), mechanical loading, as well as transcription factors (TFs) and TF-modulating proteins are indicated. Some TFs and TF-modulating proteins are negatively or positively influencing the activity of Runx2, while others are involved in the differentiation process independently of Runx2. MicroRNA species negatively affecting the differentiation of SCs elicited by GFs and/or TFs are depicted (see especially microRNAs 29, 125, 133, and 135). The osteoblast secretes matrix proteins, whose gene transcripts are modulated by TFs. It also affects osteoclast differentiation and activation by secreting the opposite acting factors RANK-L and OPG. Finally, the osteoblast might be subjected to apoptosis or acquiring an osteocytic state. Osteocytes serve as a connection between the bone tissue and the nervous system, while also perceiving the mechanical load on the skeleton.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4007326&req=5

fig1: The differentiation of stem cells (SCs) towards osteoblasts. The impact of hormones and growth factors (GFs), mechanical loading, as well as transcription factors (TFs) and TF-modulating proteins are indicated. Some TFs and TF-modulating proteins are negatively or positively influencing the activity of Runx2, while others are involved in the differentiation process independently of Runx2. MicroRNA species negatively affecting the differentiation of SCs elicited by GFs and/or TFs are depicted (see especially microRNAs 29, 125, 133, and 135). The osteoblast secretes matrix proteins, whose gene transcripts are modulated by TFs. It also affects osteoclast differentiation and activation by secreting the opposite acting factors RANK-L and OPG. Finally, the osteoblast might be subjected to apoptosis or acquiring an osteocytic state. Osteocytes serve as a connection between the bone tissue and the nervous system, while also perceiving the mechanical load on the skeleton.
Mentions: The differentiation of MSCs towards osteoblasts undergoes several phases including osteoprogenitor cells, their differentiation into pre-osteoblasts and mature osteoblasts. The latter are transformed into osteocytes, which may constitute the mechano-sensing lattice and nervous system junction connecting bone to the outer “environment”2, 5, 34, 35, 36, 37, 38, 39, 40, or they are subjected to apoptosis (Figure 1). A concerted action of both positive and negative regulatory factors determines the developing phenotype of the osteoblastic cells, including the processes of bone modelling and remodelling. This involves the concerted action of secreted RANK-L and OPG, acting on osteoclastic cells2, 4, 5, 6, 41, 42. Major functional features of the osteoblast pertain to sequential synthesis and deposition of matrix proteins and enzymes necessary to complete these processes. Finally, the transition of osteoblasts to osteocytes are also modulated by several factors (Figure 1), yielding a complete and versatile cellular system, being able to adapt to various physiological conditions, when necessary2, 5, 43.

Bottom Line: These act on stem cells (SCs) recruited for lineage-specific differentiation, with cellular phenotypes representing various functions throughout their life span.The signals are rendered by hormones and growth factors (GFs) and mechanical forces ensuring proper modelling and remodelling of bone and cartilage, due to indigenous and programmed metabolism in SCs, osteoblasts, chondrocytes, as well as osteoclasts and other cell types (eg T helper cells).This review focuses on the concerted action of such signals, as well as the regulatory and/or stabilizing control circuits rendered by a class of small RNAs, designated microRNAs.The present approach to cell differentiation in vitro may vastly influence cell engineering for in vivo tissue repair.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, Institute for Basal Medical Sciences, Medical Faculty, University of Oslo, Norway. j.o.gordeladze@medisin.uio.no

ABSTRACT
Bone and cartilage are being generated de novo through concerted actions of a plethora of signals. These act on stem cells (SCs) recruited for lineage-specific differentiation, with cellular phenotypes representing various functions throughout their life span. The signals are rendered by hormones and growth factors (GFs) and mechanical forces ensuring proper modelling and remodelling of bone and cartilage, due to indigenous and programmed metabolism in SCs, osteoblasts, chondrocytes, as well as osteoclasts and other cell types (eg T helper cells).This review focuses on the concerted action of such signals, as well as the regulatory and/or stabilizing control circuits rendered by a class of small RNAs, designated microRNAs. The impact on cell functions evoked by transcription factors (TFs) via various signalling molecules, also encompassing mechanical stimulation, will be discussed featuring microRNAs as important members of an integrative system. The present approach to cell differentiation in vitro may vastly influence cell engineering for in vivo tissue repair.

Show MeSH