Osteogenic properties of human myogenic progenitor cells

Abstract

Here, we identified human myogenic progenitor cells coexpressing Pax7, a marker of muscle satellite cells and bone-specific alkaline phosphatase, a marker of osteoblasts, in regenerating muscle. To determine whether human myogenic progenitor cells are able to act as osteoprogenitor cells, we cultured both primary and immortalized progenitor cells derived from the healthy muscle of a nondystrophic woman. The undifferentiated myogenic progenitors spontaneously expressed two osteoblast-specific proteins, bone-specific alkaline phosphatase and Runx2, and were able to undergo terminal osteogenic differentiation without exposure to an exogenous inductive agent such as bone morphogenetic proteins. They also expressed the muscle lineage-specific proteins Pax7 and MyoD, and lost their osteogenic characteristics in association with terminal muscle differentiation. Both myoblastic and osteoblastic properties are thus simultaneously expressed in the human myogenic cell lineage prior to commitment to muscle differentiation. In addition, C3 transferase, a specific inhibitor of Rho GTPase, blocked myogenic but not osteogenic differentiation of human myogenic progenitor cells. These data suggest that human myogenic progenitor cells retain the capacity to act as osteoprogenitor cells that form ectopic bone spontaneously, and that Rho signaling is involved in a critical switch between myogenesis and osteogenesis in the human myogenic cell lineage.

Enhanced differentiation of human embryonic stem cells to mesenchymal progenitors by inhibition of TGF-β/activin/nodal signaling using SB-431542

“…Our data corroborate the recent findings published by Hashimoto and colleagues, (9) who have shown that human adult skeletal muscle-derived myogenic progenitors expressing known myogenic markers such as Pax7 and CD34 have the ability to differentiate ex vivo into pure MSC-like cells expressing key marker proteins for MSCs (eg, vimentin, CD44, CD73, CD146, and CD166) in combination with the key osteogenic transcription factor Runx2. This finding was confirmed by microarray analysis of hESC-derived MSCs that clearly showed downregulation of all skeletal muscle and myocyte genes ( Table 1) and upregulation of skeletal-and mesodermal-specific genes (Supplemental Fig.…”

“…For example, bone marrow-derived (3,4) or adipose tissue-derived (5,6) stromal (mesenchymal) stem cells (MSCs) or muscle-derived satellite cells (7,8) are multipotent stem cells that can differentiate, under proper ex vivo culture conditions, into osteoblasts, adipocytes, chondrocytes, or myocytes. (7,9) In addition, preliminary proof-of-concept studies suggest functional improvement of the affected organ after cell transplantation. (10,11) However, a number of factors limit the clinical use of adult stem cells in therapy (eg, the inability to obtain sufficient numbers of cells for therapy owing to inadequate numbers of cells obtained from tissue biopsies, poorly defined stem cell phenotype, and impaired growth and function owing to replicative cellular senescence during ex vivo expansion).…”

Identifying the Cellular Mechanisms Leading to Heterotopic Ossification

“…As such, these cells are commonly referred to as inducible osteoprogenitors, since their osteogenic potential is dependent on the addition of inductive agents such as BMP-2 [59]. Although, there is some evidence to suggest that human satellite cells may not require BMP-2 induction to reach an osteogenic state [60]. It has been proposed that satellite cells may contribute to the formation of ectopic bone as a result of an inability to restrict their phenotypic plasticity [58].…”

CDK4 and cyclin D1 allow human myogenic cells to recapture growth property without compromising differentiation potential

“…9 Immortalized human myogenic cells retain differentiation potential both in vivo and in vitro The cells immortalized by the forced expression of hTERT and E7 preserved the phenotypic characteristics of their parental Hu5 cells, including multipotentiality; one of the E7-expressing immortalized Hu5 cell clones, E18, retained the ability to undergo myogenic, osteogenic and adipogenic terminal differentiation. 7,9 The CDK4R24C and cyclin D1-expressing immortalized clones, KD3 and TKD1, also underwent myogenic, osteogenic and adipogenic terminal differentiation under the appropriate culture conditions (Figures 6a-c and f-h), although adipogenic differentiation was induced at relatively low efficiency.…”

“…[3][4][5] However, several previous studies strongly suggest that animal myogenic cells do not always use the same pathways to control proliferation and differentiation as human myogenic cells. 6,7 Although animal cell models certainly contribute to understanding the mechanisms of human myogenesis and muscle diseases, the precise and detailed analysis of human myogenic cells is essential for fundamental and therapeutic investigation. Unfortunately, progressively compromised differentiation potential, as well as proliferation potential, is seen in cultured human myogenic cells.…”