Markers for Identification of Postnatal Skeletal Stem Cells In Vivo

Cao, Ye; Buckels, Emma J.; Matthews, Brya G.

doi:10.1007/s11914-020-00622-2

Cited by 15 publications

(13 citation statements)

References 79 publications

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“…In the bone marrow compartment, it is well-established that the endosteal region, as well as regions near trabecular bone surfaces, are highly enriched for stem and progenitor cells, including cells of the mesenchymal or skeletal lineage (1, 2). Skeletal stem cells can be isolated from various bone compartments based on their plastic adherence, however, more recently, numerous markers have been proposed to identify or isolate skeletal progenitors prospectively (3).…”

Section: Introductionmentioning

confidence: 99%

Heterogeneity of murine periosteum progenitors involved in fracture healing

Matthews

Novak

Sbrana

et al. 2021

eLife

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The periosteum is the major source of cells involved in fracture healing. We sought to characterize progenitor cells and their contribution to bone fracture healing. The periosteum is highly enriched for progenitor cells, including Sca1+ cells, CFU-F and label-retaining cells compared to the endosteum and bone marrow. Using lineage tracing, we demonstrate that αSMA identifies long-term, slow-cycling, self-renewing osteochondroprogenitors in the adult periosteum that are functionally important for bone formation during fracture healing. In addition, Col2.3CreER-labeled osteoblast cells contribute around 10% of osteoblasts, but no chondrocytes in fracture calluses. Most periosteal osteochondroprogenitors following fracture, can be targeted by αSMACreER. Previously identified skeletal stem cell populations were common in periosteum, but contained high proportions of mature osteoblasts. We have demonstrated that the periosteum is highly enriched for skeletal progenitor cells and there is heterogeneity in the populations of cells that contribute to mature lineages during periosteal fracture healing.

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Section: Introductionmentioning

confidence: 99%

Heterogeneity of murine periosteum progenitors involved in fracture healing

Matthews

Novak

Sbrana

et al. 2021

eLife

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“…In the present study, it was difficult to ascertain whether stem cells from the cortical bone or the bone marrow played a critical role in healing the femoral defects. The concept of skeletal stem cells has recently been proposed, and various markers of differentiated subgroups of skeletal stem cells residing in the growth plate, periosteum, have already been identified [ 24 – 26 ]. BMMSCs consist of a heterogeneous cell mixture, and only a fraction of these cells possesses stem cell properties.…”

Section: Discussionmentioning

confidence: 99%

Melatonin attenuates radiation-induced cortical bone-derived stem cells injury and enhances bone repair in postradiation femoral defect model

Liang

Liao

et al. 2021

Military Med Res

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Background The healing of bone defects can be challenging for clinicians to manage, especially after exposure to ionizing radiation. In this regard, radiation therapy and accidental exposure to gamma (γ)-ray radiation have been shown to inhibit bone formation and increase the risk of fractures. Cortical bone-derived stem cells (CBSCs) are reportedly essential for osteogenic lineages, bone maintenance and repair. This study aimed to investigate the effects of melatonin on postradiation CBSCs and bone defect healing. Methods CBSCs were extracted from C57BL/6 mice and were identified by flow cytometry. Then CBSCs were subjected to 6 Gy γ-ray radiation followed by treatment with various concentrations of melatonin. The effects of exogenous melatonin on the self-renewal and osteogenic capacity of postradiation CBSCs in vitro were analyzed. The underlying mechanisms involved in genomic stability, apoptosis and oxidative stress-related signaling were further analyzed by Western blotting, flow cytometry and immunofluorescence assays. Moreover, postradiation femoral defect models were established and treated with Matrigel and melatonin. The effects of melatonin on postradiation bone healing in vivo were evaluated by micro-CT and pathological analysis. Results The decrease in radiation-induced self-renewal and osteogenic capacity were partially reversed in postradiation CBSCs treated with melatonin (P < 0.05). Melatonin maintained genomic stability, reduced postradiation CBSC apoptosis and intracellular oxidative stress, and enhanced expression of antioxidant-related enzymes (P < 0.05). Western blotting validated the anti-inflammatory effects of melatonin by downregulating interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) levels via the extracellular regulated kinase (ERK)/nuclear factor erythroid 2-related factor 2 (NRF2)/heme oxygenase-1 (HO-1) signaling pathway. Melatonin was also found to exhibit antioxidant effects via NRF2 signaling. In vivo experiments demonstrated that the newly formed bone in the melatonin plus Matrigel group had higher trabecular bone volume per tissue volume (BV/TV) and bone mineral density values with lower IL-6 and TNF-α levels than in the irradiation and the Matrigel groups (P < 0.05). Conclusion This study suggested that melatonin could protect CBSCs against γ-ray radiation and assist in the healing of postradiation bone defects.

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“…In the present study, it is di cult to tell which kind of stem cells, from cortical bone or bone marrow, play a more critical role in healing of femoral defects. In fact, the concept of skeletal stem cells were proposed and identi ed recently, and various markers were applied to differentiate subgroups of skeletal stem cells resided in growth plate, periosteum, etc [25][26][27]. Bone marrow-derive mesenchymal stem cells (BMMSCs) comprise a very heterogeneous cell mixture, only a fraction of which have stem properties.…”

Section: Discussionmentioning

confidence: 99%

Melatonin attenuates radiation-induced cortical bone-derived stem cells injury and enhances bone repair in postradiation femoral defect model

Liang

Liao

et al. 2021

Preprint

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Background Ionizing radiation poses a challenge to the healing of bone defects. Radiation therapy and accidental exposure to gamma-ray (γ-ray) radiation inhibit bone formation and increase the risk of fractures. Cortical bone-derived stem cells (CBSCs) are essential for osteogenic lineages, bone maintenance, and repair. This study aimed to investigate the effects of melatonin on postradiation CBSCs and bone defects. Methods CBSCs were extracted from C57/BL6 mice and were identified by flow cytometry. The effects of exogenous melatonin on the self-renewal and osteogenic capacity of postradiation CBSCs were detected in vitro. The underlying mechanisms in terms of genomic stability, apoptosis and oxidative stress-related signaling were further analyzed by western blotting, flow cytometry and immunofluorescence. Finally, the effects of melatonin on healing in postradiation bone defects were evaluated in vivo by micro-CT and immunohistochemical analysis. Results The radiation-induced reduced self-renewal and osteogenic capacity were partially reversed in postradiation CBSCs treated with melatonin. Melatonin maintained the genomic stability and apoptosis of postradiation CBSCs, and intracellular oxidative stress was decreased significantly while antioxidant-related enzymes were enhanced. Western blotting verified the anti-inflammatory effect of melatonin by downregulating the levels of IL-6 and TNF-α via extracellular regulated kinase (ERK)/nuclear factor erythroid 2-related factor 2 (NRF2)/heme oxygenase 1 (HO-1) signaling, distinct from its antioxidant effect via NRF2 signaling. In vivo experiments demonstrated that the newly formed bone in the melatonin plus Matrigel group had higher trabecular bone volume per tissue volume (BV/TV) and bone mineral density (BMD) values, and lower levels of IL-6 and TNF-α than those in the irradiation and the Matrigel groups. Conclusions This study suggested the potential of melatonin to protect CBSCs against γ-ray radiation and to assist the healing of postradiation bone defects.

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Markers for Identification of Postnatal Skeletal Stem Cells In Vivo

Cited by 15 publications

References 79 publications

Heterogeneity of murine periosteum progenitors involved in fracture healing

Heterogeneity of murine periosteum progenitors involved in fracture healing

Melatonin attenuates radiation-induced cortical bone-derived stem cells injury and enhances bone repair in postradiation femoral defect model

Melatonin attenuates radiation-induced cortical bone-derived stem cells injury and enhances bone repair in postradiation femoral defect model

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