scholarly journals Osteogenic and Chondrogenic Potential of Periosteum-Derived Mesenchymal Stromal Cells: Do They Hold the Key to the Future?

2021 ◽  
Vol 14 (11) ◽  
pp. 1133
Author(s):  
Madhan Jeyaraman ◽  
Sathish Muthu ◽  
Prakash Gangadaran ◽  
Rajni Ranjan ◽  
Naveen Jeyaraman ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Bone Repair ◽  
Dynamic Environment ◽  
Collagen Matrix ◽  
Mesenchymal Progenitors ◽  
The Future ◽  
Cambium Layer ◽  
Periosteal Cells

The periosteum, with its outer fibrous and inner cambium layer, lies in a dynamic environment with a niche of pluripotent stem cells for their reparative needs. The inner cambium layer is rich in mesenchymal progenitors, osteogenic progenitors, osteoblasts, and fibroblasts in a scant collagen matrix environment. Their role in union and remodeling of fracture is well known. However, the periosteum as a source of mesenchymal stem cells has not been explored in detail. Moreover, with the continuous expansion of techniques, newer insights have been acquired into the roles and regulation of these periosteal cells. From a therapeutic standpoint, the periosteum as a source of tissue engineering has gained much attraction. Apart from its role in bone repair, analysis of the bone-forming potential of periosteum-derived stem cells is lacking. Hence, this article elucidates the role of the periosteum as a potential source of mesenchymal stem cells along with their capacity for osteogenic and chondrogenic differentiation for therapeutic application in the future.

scholarly journals TRPV4-mediated calcium signaling in mesenchymal stem cells regulates aligned collagen matrix formation and vinculin tension

2019 ◽  
Vol 116 (6) ◽  
pp. 1992-1997 ◽  
Author(s):  
Christopher L. Gilchrist ◽  
Holly A. Leddy ◽  
Laurel Kaye ◽  
Natasha D. Case ◽  
Katheryn E. Rothenberg ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Intracellular Signaling ◽  
Collagen Matrix ◽  
Transient Receptor Potential Vanilloid ◽  
Fibrillar Collagen ◽  
Matrix Assembly ◽  
Collagen Formation ◽  
Signaling Events

Microarchitectural cues drive aligned fibrillar collagen deposition in vivo and in biomaterial scaffolds, but the cell-signaling events that underlie this process are not well understood. Utilizing a multicellular patterning model system that allows for observation of intracellular signaling events during collagen matrix assembly, we investigated the role of calcium (Ca2+) signaling in human mesenchymal stem cells (MSCs) during this process. We observed spontaneous Ca2+oscillations in MSCs during fibrillar collagen assembly, and hypothesized that the transient receptor potential vanilloid 4 (TRPV4) ion channel, a mechanosensitive Ca2+-permeable channel, may regulate this signaling. Inhibition of TRPV4 nearly abolished Ca2+signaling at initial stages of collagen matrix assembly, while at later times had reduced but significant effects. Importantly, blocking TRPV4 activity dramatically reduced aligned collagen fibril assembly; conversely, activating TRPV4 accelerated aligned collagen formation. TRPV4-dependent Ca2+oscillations were found to be independent of pattern shape or subpattern cell location, suggesting this signaling mechanism is necessary for aligned collagen formation but not sufficient in the absence of physical (microarchitectural) cues that force multicellular alignment. As cell-generated mechanical forces are known to be critical to the matrix assembly process, we examined the role of TRPV4-mediated Ca2+signaling in force generated across the load-bearing focal adhesion protein vinculin within MSCs using an FRET-based tension sensor. Inhibiting TRPV4 decreased tensile force across vinculin, whereas TRPV4 activation caused a dynamic unloading and reloading of vinculin. Together, these findings suggest TRPV4 activity regulates forces at cell-matrix adhesions and is critical to aligned collagen matrix assembly by MSCs.

Role of PTH1R Signaling in Prx1+ Mesenchymal Progenitors during Eruption

2020 ◽  
Vol 99 (11) ◽  
pp. 1296-1305
Author(s):  
C. Cui ◽  
R. Bi ◽  
W. Liu ◽  
S. Guan ◽  
P. Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Bone Formation ◽  
Bone Remodeling ◽  
Periodontal Ligament ◽  
Alveolar Bone ◽  
Tooth Eruption ◽  
Mesenchymal Progenitors

Tooth eruption is a complex process requiring precise interaction between teeth and adjacent tissues. Molecular analysis demonstrates that bone remodeling plays an essential role during eruption, suggesting that a parathyroid hormone 1 receptor (PTH1R) gene mutation is associated with disturbances in bone remodeling and results in primary failure of eruption (PFE). Recent research reveals the function of PTH1R signaling in mesenchymal progenitors, whereas the function of PTH1R in mesenchymal stem cells during tooth eruption remains incompletely understood. We investigated the specific role of PTH1R in Prx1+ progenitor expression during eruption. We found that Prx1+-progenitors occur in mesenchymal stem cells residing in alveolar bone marrow surrounding incisors, at the base of molars and in the dental follicle and pulp of incisors. Mice with conditional deletion of PTH1R using the Prx1 promoter exhibited arrested mandibular incisor eruption and delayed molar eruption. Micro–computed tomography, histomorphometry, and molecular analyses revealed that mutant mice had significantly reduced alveolar bone formation concomitant with downregulated gene expression of key regulators of osteogenesis in PTH1R-deficient cells. Moreover, culturing orofacial bone-marrow-derived mesenchymal stem cells (OMSCs) from Prx1Cre;PTH1Rfl/fl mice or from transfecting Cre recombinase adenovirus in OMSCs from PTH1Rfl/fl mice suggested that lack of Pth1r expression inhibited osteogenic differentiation in vitro. However, bone resorption was not affected by PTH1R ablation, indicating the observed reduced alveolar bone volume was mainly due to impaired bone formation. Furthermore, we found irregular periodontal ligaments and reduced Periostin expression in mutant incisors, implying loss of PTH1R results in aberrant differentiation of periodontal ligament cells. Collectively, these data suggest that PTH1R signaling in Prx1+ progenitors plays a critical role in alveolar bone formation and periodontal ligament development during eruption. These findings have implications for our understanding of the physiologic and pathologic function of PTH1R signaling in tooth eruption and the progression of PFE.

scholarly journals Mettl3 Regulates Osteogenic Differentiation and Alternative Splicing of Vegfa in Bone Marrow Mesenchymal Stem Cells

2019 ◽  
Vol 20 (3) ◽  
pp. 551 ◽  
Author(s):  
Cheng Tian ◽  
Yanlan Huang ◽  
Qimeng Li ◽  
Zhihui Feng ◽  
Qiong Xu
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Alternative Splicing ◽  
Osteogenic Differentiation ◽  
Bone Repair ◽  
Bone Mineralization ◽  
Sequencing Analysis ◽  
Bone Mesenchymal Stem Cells ◽  
Vast Number

Bone mesenchymal stem cells (BMSCs) can be a useful cell resource for developing biological treatment strategies for bone repair and regeneration, and their therapeutic applications hinge on an understanding of their physiological characteristics. N6-methyl-adenosine (m6A) is the most prevalent internal chemical modification of mRNAs and has recently been reported to play important roles in cell lineage differentiation and development. However, little is known about the role of m6A modification in the cell differentiation of BMSCs. To address this issue, we investigated the expression of N6-adenosine methyltransferases (Mettl3 and Mettl14) and demethylases (Fto and Alkbh5) and found that Mettl3 was upregulated in BMSCs undergoing osteogenic induction. Furthermore, we knocked down Mettl3 and demonstrated that Mettl3 knockdown decreased the expression of bone formation-related genes, such as Runx2 and Osterix. The alkaline phosphatase (ALP) activity and the formation of mineralized nodules also decreased after Mettl3 knockdown. RNA sequencing analysis revealed that a vast number of genes affected by Mettl3 knockdown were associated with osteogenic differentiation and bone mineralization. Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis revealed that the phosphatidylinositol 3-kinase/AKT (PI3K-Akt) signaling pathway appeared to be one of the most enriched pathways, and Western blotting results showed that Akt phosphorylation was significantly reduced after Mettl3 knockdown. Mettl3 has been reported to play an important role in regulating alternative splicing of mRNA in previous research. In this study, we found that Mettl3 knockdown not only reduced the expression of Vegfa but also decreased the level of its splice variants, vegfa-164 and vegfa-188, in Mettl3-deficient BMSCs. These findings might contribute to novel progress in understanding the role of epitranscriptomic regulation in the osteogenic differentiation of BMSCs and provide a promising perspective for new therapeutic strategies for bone regeneration.

scholarly journals RSP5 Positively Regulates the Osteogenic Differentiation of Mesenchymal Stem Cells by Activating the K63-Linked Ubiquitination of Akt

2020 ◽  
Vol 2020 ◽  
pp. 1-13 ◽  
Author(s):  
Changxiang Liang ◽  
Guoyan Liang ◽  
Xiaoqing Zheng ◽  
Yongxiong Huang ◽  
Shuaihao Huang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Osteogenic Differentiation ◽  
Bone Repair ◽  
Multipotent Stem Cells ◽  
Cell Therapies ◽  
Ubiquitin Protein Ligase ◽  
Promising Target ◽  
Further Development

Mesenchymal stem cells (MSCs) are multipotent stem cells that have a strong osteogenic differentiation capacity. However, the molecular mechanism underlying the osteogenic differentiation of MSCs remains largely unknown and thus hinders further development of MSC-based cell therapies for bone repair in the clinic. RSP5, also called NEDD4L (NEDD4-like E3 ubiquitin protein ligase), belongs to the HECT (homologous to E6-AP carboxyl terminus) domain-containing E3 ligase family. Nevertheless, although many studies have been conducted to elucidate the role of RSP5 in various biological processes, its effect on osteogenesis remains elusive. In this study, we demonstrated that the expression of RSP5 was elevated during the osteogenesis of MSCs and positively regulated the osteogenic capacity of MSCs by inducing K63-linked polyubiquitination and activation of the Akt pathway. Taken together, our findings suggest that RSP5 may be a promising target to improve therapeutic efficiency by using MSCs for bone regeneration and repair.

The role of mesenchymal stem cells in bone repair and regeneration

2013 ◽  
Vol 24 (3) ◽  
pp. 257-262 ◽  
Author(s):  
Pavel Šponer ◽  
Tomáš Kučera ◽  
Daniel Diaz-Garcia ◽  
Stanislav Filip
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Bone Repair

The Future Role of Mesenchymal Stem Cells in the Management of Shoulder Disorders

2013 ◽  
Vol 29 (10) ◽  
pp. 1702-1711 ◽  
Author(s):  
Knut Beitzel ◽  
Olga Solovyova ◽  
Mark P. Cote ◽  
John Apostolakos ◽  
Ryan P. Russell ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Future Role ◽  
The Future ◽  
Shoulder Disorders

Regeneration of Bone Defects Using Bioactive Glass Combined with Adipose-derived Mesenchymal Stem Cells. An experimental in vivo study

2019 ◽  
Vol 70 (6) ◽  
pp. 1983-1987
Author(s):  
Cristian Trambitas ◽  
Anca Maria Pop ◽  
Alina Dia Trambitas Miron ◽  
Dorin Constantin Dorobantu ◽  
Flaviu Tabaran ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Bioactive Glass ◽  
Bone Repair ◽  
Bone Defects ◽  
Calvarial Bone ◽  
Specific Protocol ◽  
Repair Mechanisms ◽  
Male Wistar Rats

Large bone defects are a medical concern as these are often unable to heal spontaneously, based on the host bone repair mechanisms. In their treatment, bone tissue engineering techniques represent a promising approach by providing a guide for osseous regeneration. As bioactive glasses proved to have osteoconductive and osteoinductive properties, the aim of our study was to evaluate by histologic examination, the differences in the healing of critical-sized calvarial bone defects filled with bioactive glass combined with adipose-derived mesenchymal stem cells, compared to negative controls. We used 16 male Wistar rats subjected to a specific protocol based on which 2 calvarial bone defects were created in each animal, one was filled with Bon Alive S53P4 bioactive glass and adipose-derived stem cells and the other one was considered control. At intervals of one week during the following month, the animals were euthanized and the specimens from bone defects were histologically examined and compared. The results showed that this biomaterial was biocompatible and the first signs of osseous healing appeared in the third week. Bone Alive S53P4 bioactive glass could be an excellent bone substitute, reducing the need of bone grafts.

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