The role of MyoD+ muscle progenitor cells in bone formation and repair

SummaryOne of the key issues of organogenesis is the understanding of mechanisms underlying the differentiation of progenitor cells into more specialized cells of individual tissues. Recent transcriptomic and proteomic approaches of molecular biology have led to the identification of several factors and mechanisms regulating morphogenesis at the genetic level which affect the function of already differentiated cells. In the last few years, several reports about osteoblastogenesis have been published. This review presents recent findings on the role of the most important transcription factors supporting bone formation.

Download Full-text

Reduction of Connexin 43 Attenuates Angiogenic Effects of Human Smooth Muscle Progenitor Cells via Inactivation of Akt and NF-κB Pathway

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvbaha.120.315650 ◽

2020 ◽

Author(s):

Ting-Yi Tien ◽

Yih-Jer Wu ◽

Cheng-Huang Su ◽

Hsueh-Hsiao Wang ◽

Chin-Ling Hsieh ◽

...

Keyword(s):

Smooth Muscle ◽

Protein Kinase ◽

Progenitor Cells ◽

Connexin 43 ◽

Paracrine Effects ◽

Angiogenic Potential ◽

Junction Protein ◽

Src Activation ◽

Muscle Progenitor Cells

Objective: Circulating progenitor cells possess vasculogenesis property and participate in repair of vascular injury. Cx (connexin) 43—a transmembrane protein constituting gap junctions—is involved in vascular pathology. However, the role of Cx43 in smooth muscle progenitor cells (SPCs) remained unclear. Approach and Results: Human SPCs cultured from CD34 + peripheral blood mononuclear cells expressed smooth muscle cell markers, such as smooth muscle MHC (myosin heavy chain), nonmuscle MHC, calponin, and CD140B, and Cx43 was the most abundant Cx isoform. To evaluate the role of Cx43 in SPCs, short interference RNA was used to knock down Cx43 expression. Cellular activities of SPCs were reduced by Cx43 downregulation. In addition, Cx43 downregulation attenuated angiogenic potential of SPCs in hind limb ischemia mice. Protein array and ELISA of the supernatant from SPCs showed that IL (interleukin)-6, IL-8, and HGF (hepatocyte growth factor) were reduced by Cx43 downregulation. Simultaneously, Cx43 downregulation reduced the phosphorylation of NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) and Akt (protein kinase B) pathway and reactivation of NF-κB and Akt using betulinic acid, and SC79 could restore the secretion of growth factors and cytokines. Moreover, FAK (focal adhesion kinase)-Src (proto-oncogene tyrosine-protein kinase Src) activation was increased by Cx43 downregulation, and inactivation of Akt–NF-κB could be restored by Src inhibitor (PP2), indicating that Akt–NF-κB inactivated by Cx43 downregulation arose from FAK-Src activation. Finally, the depressed cellular activities and secretion of SPCs after Cx43 downregulation were restored by FAK inhibitor PF-562271 or PP2. Conclusions: SPCs possess angiogenic potential to repair ischemic tissue mainly through paracrine effects. Gap junction protein Cx43 plays an important role in regulating cellular function and paracrine effects of SPCs through FAK-Src axis.

Download Full-text

Role of muscle progenitor cells in maintaining morphological characteristics of rat soleus muscle during gravitational unloading by means of passive stretch

Cell and Tissue Biology ◽

10.1134/s1990519x08020120 ◽

2008 ◽

Vol 2 (2) ◽

pp. 176-183

Author(s):

M. V. Tarakina ◽

O. V. Turtikova ◽

T. L. Nemirovskaya ◽

A. A. Kokontsev ◽

B. S. Shenkman

Keyword(s):

Progenitor Cells ◽

Soleus Muscle ◽

Morphological Characteristics ◽

Gravitational Unloading ◽

Rat Soleus Muscle ◽

Muscle Progenitor Cells ◽

Passive Stretch

Download Full-text

Transcriptional landscape of myogenesis from human pluripotent stem cells reveals a key role of TWIST1 in maintenance of skeletal muscle progenitors

eLife ◽

10.7554/elife.46981 ◽

2020 ◽

Vol 9 ◽

Cited By ~ 1

Author(s):

In Young Choi ◽

Hotae Lim ◽

Hyeon Jin Cho ◽

Yohan Oh ◽

Bin-Kuan Chou ◽

...

Keyword(s):

Skeletal Muscle ◽

Stem Cells ◽

Progenitor Cells ◽

Pluripotent Stem Cells ◽

Expression Profiles ◽

Human Pluripotent Stem Cells ◽

Knock Out ◽

Muscle Progenitor Cells ◽

Transcriptional Landscape

Generation of skeletal muscle cells with human pluripotent stem cells (hPSCs) opens new avenues for deciphering essential, but poorly understood aspects of transcriptional regulation in human myogenic specification. In this study, we characterized the transcriptional landscape of distinct human myogenic stages, including OCT4::EGFP+ pluripotent stem cells, MSGN1::EGFP+ presomite cells, PAX7::EGFP+ skeletal muscle progenitor cells, MYOG::EGFP+ myoblasts, and multinucleated myotubes. We defined signature gene expression profiles from each isolated cell population with unbiased clustering analysis, which provided unique insights into the transcriptional dynamics of human myogenesis from undifferentiated hPSCs to fully differentiated myotubes. Using a knock-out strategy, we identified TWIST1 as a critical factor in maintenance of human PAX7::EGFP+ putative skeletal muscle progenitor cells. Our data revealed a new role of TWIST1 in human skeletal muscle progenitors, and we have established a foundation to identify transcriptional regulations of human myogenic ontogeny (online database can be accessed in http://www.myogenesis.net/).

Download Full-text

Role of Adult Tissue-Derived Pluripotent Stem Cells in Bone Regeneration

Stem Cell Reviews and Reports ◽

10.1007/s12015-019-09943-x ◽

2019 ◽

Vol 16 (1) ◽

pp. 198-211

Author(s):

Liudmila Leppik ◽

K. Sielatycka ◽

D. Henrich ◽

Z. Han ◽

H. Wang ◽

...

Keyword(s):

Stem Cells ◽

Bone Formation ◽

Progenitor Cells ◽

Bone Healing ◽

Pluripotent Stem Cells ◽

Mononuclear Cells ◽

Fibrous Tissue ◽

Female Rats ◽

Post Surgery

Abstract Background Bone marrow-derived mononuclear cells (BM-MNC) consist of a heterogeneous mix of mesenchymal stem cells (MSC), hematopoietic progenitor cells (HPC), endothelial progenitor cells (EPC), monocytes, lymphocytes and pluripotent stem cells. Whereas the importance of MSC and EPC has been well documented in bone healing and regeneration studies, the role of pluripotent stem cells is still poorly understood. In the present study we evaluated if and how Very Small Embryonic Like cells (VSEL), isolated from rat BM-MNC, contribute to bone healing. Methods Large bone defects were made in the femurs of 38 Sprague Dawley female rats and treated with β-TCP scaffold granules seeded with male VSEL; BM-MNC, VSEL-depleted BM-MNC or scaffold alone, and bone healing was evaluated at 8 weeks post-surgery. Results Bone healing was significantly increased in defects treated with VSEL and BM-MNC, compared to defects treated with VSEL-depleted BM-MNC. Donor cells were detected in new bone tissue, in all the defects treated with cells, and in fibrous tissue only in defects treated with VSEL-depleted BM-MNC. The number of CD68+ cells was the highest in the VSEL-depleted group, whereas the number of TRAP positive cells was the lowest in this group. Conclusions Based on the results, we can conclude that VSEL play a role in BM-MNC induced bone formation. In our rat femur defect model, in defects treated with VSEL-depleted BM-MNC, osteoclastogenesis and bone formation were decreased, and foreign body reaction was increased.

Download Full-text