Molecular mechanisms of mesenchymal stem cell differentiation towards osteoblasts

Abstract

Bone is a dynamic tissue that is constantly renewed by the coordinated action of two cell types, i.e., the bone-resorbing osteoclasts and the bone-forming osteoblasts. However, in some circumstances, bone regeneration exceeds bone self repair capacities. This is notably often the case after bone fractures, osteolytic bone tumor surgery, or osteonecrosis. In this regard, bone tissue engineering with autologous or allogenic mesenchymal stem cells (MSCs) is been widely developed. MSCs can be isolated from bone marrow or other tissues such as adipose tissue or umbilical cord, and can be implanted in bone defects with or without prior amplification and stimulation. However, the outcome of most pre-clinical studies remains relatively disappointing. A better understanding of the successive steps and molecular mechanisms involved in MSC-osteoblastic differentiation appears to be crucial to optimize MSC-bone therapy. In this review, we first present the important growth factors that stimulate osteoblastogenesis. Then we review the main transcription factors that modulate osteoblast differentiation, and the microRNAs (miRs) that inhibit their expression. Finally, we also discuss articles dealing with the use of these factors and miRs in the development of new bone MSC therapy strategies. We particularly focus on the studies using human MSCs, since significant differences exist between osteoblast differentiation mechanisms in humans and mice for instance.

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“…Interestingly, β-catenin is known to regulate proliferation and differentiation of BM-MSC [46] and the expression of an activated form of β-catenin in mouse osteoblasts resulted in the development of MDS and secondary AML in mice [47]. Remarkably, the presence or absence of p53 in these leukemia cells had a different impact in the GEP of BM-MSC.…”

Purinergic and Store-Operated Ca2+ Signaling Mechanisms in Mesenchymal Stem Cells and Their Roles in ATP-Induced Stimulation of Cell Migration

“…Mesenchymal stem cells (MSCs) exhibit an ability to differentiate into osteoblasts, adipocytes, and chondrocytes [9][10][11]. These multipotent stem cells are readily isolated from various tissues, including bone marrow (BM-MSCs), adipose tissues (AT-MSCs), and dental pulp (DP-MSCs) and have been extensively explored as promising cell sources for therapeutic applications such as tissue regeneration and cellbased therapies in addition to being used in understanding tissue homeostasis [12][13][14][15][16]. Accumulating evidence shows that MSCs release ATP constitutively or in response to mechanical stimulation [17][18][19][20].…”

The “soft” side of the bone: unveiling its endocrine functions

“…In agreement with this finding, cleidocranial dysplasia (CCD), an autosomal-dominant disease characterized by abnormal intramembranous ossification, is caused by Runx2 mutations [23]. Runx2 is considered an osteoblast-controlling master gene, as it upregulates osteoblast-specific genes including Collagen 1A1 (COLIA1), Alkaline Phosphatase (ALP), Bone Sialo Protein (BSP) and BGLAP (also known as Ocn, osteocalcin) [24].…”