Identification of Functionally Distinct Mx1+αSMA+ Periosteal Skeletal Stem Cells

Ortinau, Laura; Wang, Hamilton; Lei, Kevin; Deveza, Lorenzo; Jeong, Youngjae; Hara, Yannis; Grafe, Ingo; Rosenfeld, Scott; Lee, Dongjun; Lee, Brendan; Scadden, David T.; Park, Dongsu

doi:10.1016/j.stem.2019.11.003

Cited by 158 publications

(175 citation statements)

References 40 publications

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“…4G). Some cells activated Col2.3GFP indicating some differentiation into osteoblasts, similar to a recent study (20). We also investigated whether αSMA-labeled cells contained LRCs (Fig.…”

Section: αSma Identifies Transplantable Osteoprogenitorssupporting

confidence: 74%

“…Interestingly, they report the absence of αSMA+ LRCs, however many antibodies to αSMA stain perivascular cells in larger blood vessels, but do not detect αSMA+ cells in the cambium layer of the periosteum. The αSMA+ cells in the cambium layer appear to be the cell subset involved in fracture healing (20,39). Label-retention may be a useful tool to enrich for periosteal stem cells in ex vivo assays, although more robust assays for testing self-renewal such as serial transplantation are required.…”

Section: Discussionmentioning

confidence: 99%

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Heterogeneity of murine periosteum progenitors involved in fracture healing

Matthews

Novak

Sbrana

et al. 2020

Preprint

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The periosteum is the major source of cells involved in fracture healing. We sought to characterize differences in progenitor cell populations between periosteum and other bone compartments, and identify periosteal cells involved in fracture healing. The periosteum is highly enriched for progenitor cells, including Sca1+ cells, CFU-F and label-retaining cells. Lineage tracing with αSMACreER identifies periosteal cells that contribute to >80% of osteoblasts and ~40% of chondrocytes following fracture.A subset of αSMA+ cells are quiescent long-term injury-responsive progenitors. Ablation of αSMA+ cells impairs fracture callus formation. In addition, committed osteoblast-lineage cells contributed around 10% of osteoblasts, but no chondrocytes in fracture calluses. Most periosteal progenitors, particularly those that form osteoblasts, can be targeted by αSMACreER. We have demonstrated that the periosteum is highly enriched for skeletal stem and progenitor cells and there is heterogeneity in the populations of cells that contribute to mature lineages during periosteal fracture healing.

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“…4G). Some cells activated Col2.3GFP indicating some differentiation into osteoblasts, similar to a recent study (20). We also investigated whether αSMA-labeled cells contained LRCs (Fig.…”

Section: αSma Identifies Transplantable Osteoprogenitorssupporting

confidence: 74%

Section: Discussionmentioning

confidence: 99%

Heterogeneity of murine periosteum progenitors involved in fracture healing

Matthews

Novak

Sbrana

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…[166][167][168][169] Lineage tracing studies of several other periosteal skeletal stem cell markers, such as αSMA, Mx1, Cathepsin K, and Osterix, support that these cells play an important role in intramembranous bone regeneration following long bone fracture healing and stress fracture healing. 130,[170][171][172][173][174][175][176] The presence of these skeletal stem cells may be restricted to the periosteum, as the response from endosteal surface to rhBMP2 is different from the response from periosteum during stabilized fracture healing. 177 Also, Prx1 and Osterix expressing skeletal stem cells contribute to intramembranous bone regeneration in cortical bone defect models.…”

Section: Skeletal Stem Cells That Contribute To Intramembranous Bonmentioning

confidence: 99%

How faithfully does intramembranous bone regeneration recapitulate embryonic skeletal development?

Sumner

2020

Developmental Dynamics

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Postnatal intramembranous bone regeneration plays an important role during a wide variety of musculoskeletal regeneration processes such as fracture healing, joint replacement and dental implant surgery, distraction osteogenesis, stress fracture healing, and repair of skeletal defects caused by trauma or resection of tumors. The molecular basis of intramembranous bone regeneration has been interrogated using rodent models of most of these conditions. These studies reveal that signaling pathways such as Wnt, TGFβ/BMP, FGF, VEGF, and Notch are invoked, reminiscent of embryonic development of membranous bone. Discoveries of several skeletal stem cell/progenitor populations using mouse genetic models also reveal the potential sources of postnatal intramembranous bone regeneration. The purpose of this review is to compare the underlying molecular signals and progenitor cells that characterize embryonic development of membranous bone and postnatal intramembranous bone regeneration.

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“…14 Many works have attempted to investigate the periosteal stem cells and determine the cell types. [15][16][17] However, the identity of periosteal stem cells remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Periosteum progenitors could stimulate bone regeneration in aged murine bone defect model

Xiao

Wang

Zhang

et al. 2020

J Cellular Molecular Medi

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Periosteal stem cells are critical for bone regeneration, while the numbers will decrease with age. This study focused on whether Prx1+ cell, a kind of periosteal stem cell, could stimulate bone regeneration in aged mice. Four weeks and 12 months old Prx1CreER‐GFP; Rosa26tdTomato mice were used to reveal the degree of Prx1+ cells participating in the femoral fracture healing procedure. One week, 8 weeks, 12 and 24 months old Prx1CreER‐GFP mice were used to analyse the real‐time distribution of Prx1+ cells. Twelve months old C57BL/6 male mice (n = 96) were used to create the bone defect model and, respectively, received hydrogel, hydrogel with Prx1− mesenchymal stem cells and hydrogel with Prx1+ cells. H&E staining, Synchrotron radiation‐microcomputed tomography and mechanical test were used to analyse the healing results. The results showed that tdTomato+ cells were involved in bone regeneration, especially in young mice. At the same time, GFP+ cells decreased significantly with age. The Prx1+ cells group could significantly improve bone regeneration in the murine bone defect model via directly differentiating into osteoblasts and had better osteogenic differentiation ability than Prx1− mesenchymal stem cells. Our finding revealed that the quantity of Prx1+ cells might account for decreased bone regeneration ability in aged mice, and transplantation of Prx1+ cells could improve bone regeneration at the bone defect site.

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Identification of Functionally Distinct Mx1+αSMA+ Periosteal Skeletal Stem Cells

Cited by 158 publications

References 40 publications

Heterogeneity of murine periosteum progenitors involved in fracture healing

Heterogeneity of murine periosteum progenitors involved in fracture healing

How faithfully does intramembranous bone regeneration recapitulate embryonic skeletal development?

Periosteum progenitors could stimulate bone regeneration in aged murine bone defect model

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