Skeletal stem cells: a game changer of skeletal biology and regenerative medicine?

Qiaoling Zhu, Lei Ding, Rui Yue

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Life Medicine ›› 2022, Vol. 1 ›› Issue (3) : 294-306. DOI: 10.1093/lifemedi/lnac038
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Skeletal stem cells: a game changer of skeletal biology and regenerative medicine?

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Abstract

Skeletal stem cells (SSCs) were originally discovered in the bone marrow stroma. They are capable of self-renewal and multilineage differentiation into osteoblasts, chondrocytes, adipocytes, and stromal cells. Importantly, these bone marrow SSCs localize in the perivascular region and highly express hematopoietic growth factors to create the hematopoietic stem cell (HSC) niche. Thus, bone marrow SSCs play pivotal roles in orchestrating osteogenesis and hematopoiesis. Besides the bone marrow, recent studies have uncovered diverse SSC populations in the growth plate, perichondrium, periosteum, and calvarial suture at different developmental stages, which exhibit distinct differentiation potential under homeostatic and stress conditions. Therefore, the current consensus is that a panel of region-specific SSCs collaborate to regulate skeletal development, maintenance, and regeneration. Here, we will summarize recent advances of SSCs in long bones and calvaria, with a special emphasis on the evolving concept and methodology in the field. We will also look into the future of this fascinating research area that may ultimately lead to effective treatment of skeletal disorders.

Keywords

skeletal stem cells / hematopoietic stem cells / bone marrow microenvironment / skeletogenesis / regenerative medicine

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Qiaoling Zhu, Lei Ding, Rui Yue. Skeletal stem cells: a game changer of skeletal biology and regenerative medicine?. Life Medicine, 2022, 1(3): 294‒306 https://doi.org/10.1093/lifemedi/lnac038

References

[1]
FukumotoS, MartinTJ. Bone as an endocrine organ. Trends Endocrinol Metab 2009;20:230–6.
CrossRef Google scholar
[2]
GunturAR, RosenCJ. Bone as an endocrine organ. Endocr Pract 2012;18:758–62.
CrossRef Google scholar
[3]
KarsentyG, OlsonEN. Bone and muscle endocrine functions: unexpected paradigms of inter-organ communication. Cell 2016;164:1248–56.
CrossRef Google scholar
[4]
ZhouBO, YueR, MurphyMM, et al. Leptin-receptor-expressing mesenchymal stromal cells represent the main source of bone formed by adult bone marrow. Cell Stem Cell 2014;15:154–68.
CrossRef Google scholar
[5]
ComazzettoS, ShenB, MorrisonSJ. Niches that regulate stem cells and hematopoiesis in adult bone marrow. Dev Cell 2021;56:1848–60.
CrossRef Google scholar
[6]
ConfavreuxCB. Bone: from a reservoir of minerals to a regulator of energy metabolism. Kidney Int 2011;79121:S14–19.
CrossRef Google scholar
[7]
FriedensteinAJ, Chailakhyan RK, GerasimovUV. Bone marrow osteogenic stem cells: in vitro cultivation and transplantation in diffusion chambers. Cell Tissue Kinet 1987;20:263–72.
CrossRef Google scholar
[8]
OwenM, Friedenstein AJ. Stromal stem cells: marrow-derived osteogenic precursors. Ciba Found Symp 1988;136:42–60.
CrossRef Google scholar
[9]
CaplanAI. Mesenchymal stem cells. J Orthop Res 1991;9:641–50.
CrossRef Google scholar
[10]
KrebsbachPH, Kuznetsov SA, BiancoP, et al. Bone marrow stromal cells: characterization and clinical application. Crit Rev Oral Biol Med 1999;10:165–81.
CrossRef Google scholar
[11]
LefebvreV, Bhattaram P. Vertebrate skeletogenesis. Curr Top Dev Biol 2010;90:291–317.
CrossRef Google scholar
[12]
WilliamsS, Alkhatib B, SerraR. Development of the axial skeleton and intervertebral disc. Curr Top Dev Biol 2019;133:49–90.
CrossRef Google scholar
[13]
GaleaGL, ZeinMR, AllenS, et al. Making and shaping endochondral and intramembranous bones. Dev Dyn 2021;250:414–49.
CrossRef Google scholar
[14]
NodenDM, Trainor PA. Relations and interactions between cranial mesoderm and neural crest populations. J Anat 2005;207:575–601.
CrossRef Google scholar
[15]
JinSW, SimKB, KimSD. Development and growth of the normal cranial vault: an embryologic review. J Korean Neurosurg Soc 2016;59:192–6.
CrossRef Google scholar
[16]
BerendsenAD, OlsenBR. Bone development. Bone 2015;80:14–18.
CrossRef Google scholar
[17]
SalhotraA, ShahHN, LeviB, et al. Mechanisms of bone development and repair. Nat Rev Mol Cell Biol 2020;21:696–711.
CrossRef Google scholar
[18]
MaesC, Kobayashi T, SeligMK, et al. Osteoblast precursors, but not mature osteoblasts, move into developing and fractured bones along with invading blood vessels. Dev Cell 2010;19:329–44.
CrossRef Google scholar
[19]
OnoN, OnoW, MizoguchiT, et al. Vasculature-associated cells expressing nestin in developing bones encompass early cells in the osteoblast and endothelial lineage. Dev Cell 2014;29:330–9.
CrossRef Google scholar
[20]
YangL, TsangKY, TangHC, et al. Hypertrophic chondrocytes can become osteoblasts and osteocytes in endochondral bone formation. Proc Natl Acad Sci USA 2014;111:12097–102.
CrossRef Google scholar
[21]
ZhouX, von der Mark K, HenryS, et al. Chondrocytes transdifferentiate into osteoblasts in endochondral bone during development, postnatal growth and fracture healing in mice. PLoS Genet 2014;10:e1004820.
CrossRef Google scholar
[22]
OnoN, OnoW, NagasawaT, et al. A subset of chondrogenic cells provides early mesenchymal progenitors in growing bones. Nat Cell Biol 2014;16:1157–67.
CrossRef Google scholar
[23]
HallBK, MiyakeT. The membranous skeleton: the role of cell condensations in vertebrate skeletogenesis. Anat Embryol (Berl) 1992;186:107–24.
CrossRef Google scholar
[24]
ChaiY, JiangX, ItoY, et al. Fate of the mammalian cranial neural crest during tooth and mandibular morphogenesis. Development 2000;127:1671–9.
CrossRef Google scholar
[25]
QuartoN, WanDC, KwanMD, et al. Origin matters: differences in embryonic tissue origin and wnt signaling determine the osteogenic potential and healing capacity of frontal and parietal calvarial bones. J Bone Miner Res 2010;25:1680–94.
CrossRef Google scholar
[26]
HolmbeckK, BiancoP, CaterinaJ, et al. MT1-MMP-deficient mice develop dwarfism, osteopenia, arthritis, and connective tissue disease due to inadequate collagen turnover. Cell 1999;99:81–92.
CrossRef Google scholar
[27]
HolmbeckK, BiancoP, ChrysovergisK, et al. MT1-MMP-dependent, apoptotic remodeling of unmineralized cartilage: a critical process in skeletal growth. J Cell Biol 2003;163:661–71.
CrossRef Google scholar
[28]
FosterJW, Dominguez-Steglich MA, GuioliS, et al. Campomelic dysplasia and autosomal sex reversal caused by mutations in an sry-related gene. Nature 1994;372:525–30.
CrossRef Google scholar
[29]
AkiyamaH, Chaboissier M-C, MartinJF, et al. The transcription factor Sox9 has essential roles in successive steps of the chondrocyte differentiation pathway and is required for expression of sox5 and sox6. Genes Dev 2002;16:2813–28.
CrossRef Google scholar
[30]
OttoF, Thornell AP, CromptonT, et al. Cbfa1, a candidate gene for cleidocranial dysplasia syndrome, is essential for osteoblast differentiation and bone development. Cell 1997;89:765–71.
CrossRef Google scholar
[31]
InadaM, YasuiT, NomuraS, et al. Maturational disturbance of chondrocytes in Cbfa1-deficient mice. Dev Dyn 1999;214:279–90.
CrossRef Google scholar
[32]
SinhaKM, ZhouX. Genetic and molecular control of osterix in skeletal formation. J Cell Biochem 2013;114:975–84.
CrossRef Google scholar
[33]
BiancoP, RobeyPG. Skeletal stem cells. Development 2015;142:1023–7.
CrossRef Google scholar
[34]
PittengerMF, MackayAM, BeckSC, et al. Multilineage potential of adult human mesenchymal stem cells. Science 1999;284:143–7.
CrossRef Google scholar
[35]
GulatiGS, MurphyMP, MarecicO, et al. Isolation and functional assessment of mouse skeletal stem cell lineage. Nat Protoc 2018;13:1294–309.
CrossRef Google scholar
[36]
MaruyamaT, JeongJ, SheuT-J, et al. Stem cells of the suture mesenchyme in craniofacial bone development, repair and regeneration. Nat Commun 2016;7:10526.
CrossRef Google scholar
[37]
DebnathS, Yallowitz AR, McCormickJ, et al. Discovery of a periosteal stem cell mediating intramembranous bone formation. Nature 2018;562:133–9.
CrossRef Google scholar
[38]
MurphyMP, KoepkeLS, LopezMT, et al. Articular cartilage regeneration by activated skeletal stem cells. Nat Med 2020;26:1583–92.
CrossRef Google scholar
[39]
AmbrosiTH, Marecic O, McArdleA, et al. Aged skeletal stem cells generate an inflammatory degenerative niche. Nature 2021;597:256–62.
CrossRef Google scholar
[40]
HeJ, YanJ, WangJ, et al. Dissecting human embryonic skeletal stem cell ontogeny by single-cell transcriptomic and functional analyses. Cell Res 2021;31:742–57.
CrossRef Google scholar
[41]
MoC, GuoJ, QinJ, et al. Single-cell transcriptomics of LepR-positive skeletal cells reveals heterogeneous stress-dependent stem and progenitor pools. EMBO J 2022;41:e108415.
CrossRef Google scholar
[42]
StegenS, Laperre K, EelenG, et al. Hif-1alpha metabolically controls collagen synthesis and modification in chondrocytes. Nature 2019;565:511–5.
CrossRef Google scholar
[43]
ZbrodowskiA, MartyFM, GümenerR, et al. Blood supply of the subcutaneous tissue of the upper limb and its importance in the subcutaneous flap. J Hand Surg Br 1987;12:189–93.
CrossRef Google scholar
[44]
CunhaGR, BaskinL. Use of sub-renal capsule transplantation in developmental biology. Differentiation 2016;91:4–9.
CrossRef Google scholar
[45]
ItoM, Hiramatsu H, KobayashiK, et al. Nod/scid/gamma(c)(null) mouse: an excellent recipient mouse model for engraftment of human cells. Blood 2002;100:3175–82.
CrossRef Google scholar
[46]
ShultzLD, Goodwin N, IshikawaF, et al. Subcapsular transplantation of tissue in the kidney. Cold Spring Harb Protoc 2014;2014:737–40.
CrossRef Google scholar
[47]
SchmidtKM, Geissler EK, LangSA. Subcutaneous murine xenograft models: a critical tool for studying human tumor growth and angiogenesis in vivo. Methods Mol Biol 2016;1464:129–37.
CrossRef Google scholar
[48]
KuhnR, TorresRM. Cre/loxp recombination system and gene targeting. Methods Mol Biol 2002;180:175–204.
CrossRef Google scholar
[49]
SongAJ, Palmiter RD. Detecting and avoiding problems when using the Cre-lox system. Trends Genet 2018;34:333–40.
CrossRef Google scholar
[50]
HeL, LiY, LiY, et al. Enhancing the precision of genetic lineage tracing using dual recombinases. Nat Med 2017;23:1488–98.
CrossRef Google scholar
[51]
ShuHS, LiuYL, TangXT, et al. Tracing the skeletal progenitor transition during postnatal bone formation. Cell Stem Cell 2021;28:2122–36.e3.
CrossRef Google scholar
[52]
AmbrosiTH, Longaker MT, ChanCKF. A revised perspective of skeletal stem cell biology. Front Cell Dev Biol 2019;7:189.
CrossRef Google scholar
[53]
TikhonovaAN, Dolgalev I, HuH, et al. The bone marrow microenvironment at single-cell resolution. Nature 2019;569:222–8.
CrossRef Google scholar
[54]
ZhongL et al. Single cell transcriptomics identifies a unique adipose lineage cell population that regulates bone marrow environment. Elife 2020;9:e54695.
CrossRef Google scholar
[55]
FriedensteinAJ, Piatetzky S, II, PetrakovaKV. Osteogenesis in transplants of bone marrow cells. J Embryol Exp Morphol 1966;16:381–90.
CrossRef Google scholar
[56]
FriedensteinAJ, Petrakova KV, KurolesovaAI, et al. Heterotopic of bone marrow. Analysis of precursor cells for osteogenic and hematopoietic tissues. Transplantation 1968;6:230–47.
CrossRef Google scholar
[57]
FriedensteinAJ, Chailakhjan RK, LalykinaKS. The development of fibroblast colonies in monolayer cultures of guinea-pig bone marrow and spleen cells. Cell Tissue Kinet 1970;3:393–403.
CrossRef Google scholar
[58]
FriedensteinAJ, Chailakhyan RK, LatsinikNV, et al. Stromal cells responsible for transferring the microenvironment of the hemopoietic tissues. Cloning in vitro and retransplantation in vivo. Transplantation 1974;17:331–40.
CrossRef Google scholar
[59]
DominiciM, Le Blanc K, MuellerI, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The international society for cellular therapy position statement. Cytotherapy 2006;8:315–7.
CrossRef Google scholar
[60]
BiancoP, RobeyPG, SimmonsPJ. Mesenchymal stem cells: revisiting history, concepts, and assays. Cell Stem Cell 2008;2:313–9.
CrossRef Google scholar
[61]
KernS, Eichler H, StoeveJ, et al. Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem Cells 2006;24:1294–301.
CrossRef Google scholar
[62]
LiX, BaiJ, JiX, et al. Comprehensive characterization of four different populations of human mesenchymal stem cells as regards their immune properties, proliferation and differentiation. Int J Mol Med 2014;34:695–704.
CrossRef Google scholar
[63]
CaplanAI. Mesenchymal stem cells: time to change the name!. Stem Cells Transl Med 2017;6:1445–51.
CrossRef Google scholar
[64]
KuznetsovSA, Krebsbach PH, SatomuraK, et al. Single-colony derived strains of human marrow stromal fibroblasts form bone after transplantation in vivo. J Bone Miner Res 1997;12:1335–47.
CrossRef Google scholar
[65]
SacchettiB, FunariA, MichienziS, et al. Self-renewing osteoprogenitors in bone marrow sinusoids can organize a hematopoietic microenvironment. Cell 2007;131:324–36.
CrossRef Google scholar
[66]
DerubeisAR, Mastrogiacomo M, CanceddaR, et al. Osteogenic potential of rat spleen stromal cells. Eur J Cell Biol 2003;82:175–81.
CrossRef Google scholar
[67]
UezumiA, FukadaS, YamamotoN, et al. Mesenchymal progenitors distinct from satellite cells contribute to ectopic fat cell formation in skeletal muscle. Nat Cell Biol 2010;12:143–52.
CrossRef Google scholar
[68]
TodeschiMR, El Backly R, CapelliC, et al. Transplanted umbilical cord mesenchymal stem cells modify the in vivo microenvironment enhancing angiogenesis and leading to bone regeneration. Stem Cells Dev 2015;24:1570–81.
CrossRef Google scholar
[69]
DingL, Saunders TL, EnikolopovG, et al. Endothelial and perivascular cells maintain haematopoietic stem cells. Nature 2012;481:457–62.
CrossRef Google scholar
[70]
DingL, Morrison SJ. Haematopoietic stem cells and early lymphoid progenitors occupy distinct bone marrow niches. Nature 2013;495:231–5.
CrossRef Google scholar
[71]
GreenbaumA, HsuYS, DayRB, et al. CXCL12 in early mesenchymal progenitors is required for haematopoietic stem-cell maintenance. Nature 2013;495:227–30.
CrossRef Google scholar
[72]
Munoz-GarciaJ, Cochonneau D, Télétchéa S, et al. The twin cytokines interleukin-34 and csf-1: masterful conductors of macrophage homeostasis. Theranostics 2021;11:1568–93.
CrossRef Google scholar
[73]
EmotoT, LuJ, SivasubramaniyamT, et al. Colony stimulating factor-1 producing endothelial cells and mesenchymal stromal cells maintain monocytes within a perivascular bone marrow niche. Immunity 2022;55:862–78.e8.
CrossRef Google scholar
[74]
KongYY, Yoshida H, SarosiI, et al. Opgl is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis. Nature 1999;397:315–23.
CrossRef Google scholar
[75]
YasudaH, ShimaN, NakagawaN, et al. Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to trance/rankl. Proc Natl Acad Sci USA 1998;95:3597–602.
CrossRef Google scholar
[76]
YoshidaH, Hayashi S, KunisadaT, et al. The murine mutation osteopetrosis is in the coding region of the macrophage colony stimulating factor gene. Nature 1990;345:442–4.
CrossRef Google scholar
[77]
PedersonL, RuanM, WestendorfJJ, et al. Regulation of bone formation by osteoclasts involves wnt/bmp signaling and the chemokine sphingosine-1-phosphate. Proc Natl Acad Sci USA 2008;105:20764–9.
CrossRef Google scholar
[78]
IshiiM, EgenJG, KlauschenF, et al. Sphingosine-1-phosphate mobilizes osteoclast precursors and regulates bone homeostasis. Nature 2009;458:524–8.
CrossRef Google scholar
[79]
MorikawaS, Mabuchi Y, KubotaY, et al. Prospective identification, isolation, and systemic transplantation of multipotent mesenchymal stem cells in murine bone marrow. J Exp Med 2009;206:2483–96.
CrossRef Google scholar
[80]
SugiyamaT, KoharaH, NodaM, et al. Maintenance of the hematopoietic stem cell pool by CXCL12-CXCR4 chemokine signaling in bone marrow stromal cell niches. Immunity 2006;25:977–88.
CrossRef Google scholar
[81]
OmatsuY, Sugiyama T, KoharaH, et al. The essential functions of adipo-osteogenic progenitors as the hematopoietic stem and progenitor cell niche. Immunity 2010;33:387–99.
CrossRef Google scholar
[82]
Mendez-FerrerS, Michurina TV, FerraroF, et al. Mesenchymal and haematopoietic stem cells form a unique bone marrow niche. Nature 2010;466:829–34.
CrossRef Google scholar
[83]
MizoguchiT, PinhoS, AhmedJ, et al. Osterix marks distinct waves of primitive and definitive stromal progenitors during bone marrow development. Dev Cell 2014;29:340–9.
CrossRef Google scholar
[84]
YueR, ZhouBO, ShimadaIS, et al. Leptin receptor promotes adipogenesis and reduces osteogenesis by regulating mesenchymal stromal cells in adult bone marrow. Cell Stem Cell 2016;18:782–96.
CrossRef Google scholar
[85]
OmatsuY, SeikeM, SugiyamaT, et al. Foxc1 is a critical regulator of haematopoietic stem/progenitor cell niche formation. Nature 2014;508:536–40.
CrossRef Google scholar
[86]
SeikeM, OmatsuY, WatanabeH, et al. Stem cell niche-specific ebf3 maintains the bone marrow cavity. Genes Dev 2018;32:359–72.
CrossRef Google scholar
[87]
YueR, ShenB, MorrisonSJ. Clec11a/osteolectin is an osteogenic growth factor that promotes the maintenance of the adult skeleton. Elife 2016;5:e18782.
CrossRef Google scholar
[88]
ShenB et al. Integrin alpha11 is an osteolectin receptor and is required for the maintenance of adult skeletal bone mass. Elife 2019;8:e42274.
CrossRef Google scholar
[89]
WeiH, XuY, WangY, et al. Identification of fibroblast activation protein as an osteogenic suppressor and anti-osteoporosis drug target. Cell Rep 2020;33:108252.
CrossRef Google scholar
[90]
ZhangJ et al. The effect of parathyroid hormone on osteogenesis is mediated partly by osteolectin. Proc Natl Acad Sci USA 2021;118:e2026176118.
CrossRef Google scholar
[91]
ShenB, Tasdogan A, UbellackerJM, et al. A mechanosensitive peri-arteriolar niche for osteogenesis and lymphopoiesis. Nature 2021;591:438–44.
CrossRef Google scholar
[92]
BaryawnoN, Przybylski D, KowalczykMS, et al. A cellular taxonomy of the bone marrow stroma in homeostasis and leukemia. Cell 2019;177:1915–32.e16.
CrossRef Google scholar
[93]
BaccinC, Al-Sabah J, VeltenL, et al. Combined single-cell and spatial transcriptomics reveal the molecular, cellular and spatial bone marrow niche organization. Nat Cell Biol 2020;22:38–48.
CrossRef Google scholar
[94]
LeimkuhlerNB, GleitzHFE, RonghuiL, et al. Heterogeneous bone-marrow stromal progenitors drive myelofibrosis via a druggable alarmin axis. Cell Stem Cell 2021;28:637–52.e8.
CrossRef Google scholar
[95]
AmbrosiTH, Scialdone A, GrajaA, et al. Adipocyte accumulation in the bone marrow during obesity and aging impairs stem cell-based hematopoietic and bone regeneration. Cell Stem Cell 2017;20:771–84.e6.
CrossRef Google scholar
[96]
FarnumCE, Wilsman NJ. Morphologic stages of the terminal hypertrophic chondrocyte of growth plate cartilage. Anat Rec 1987;219:221–32.
CrossRef Google scholar
[97]
GibsonG, LinDL, RoqueM. Apoptosis of terminally differentiated chondrocytes in culture. Exp Cell Res 1997;233:372–82.
CrossRef Google scholar
[98]
GibsonG. Active role of chondrocyte apoptosis in endochondral ossification. Microsc Res Tech 1998;43:191–204.
CrossRef Google scholar
[99]
CheungJO, GrantME, JonesCJP, et al. Apoptosis of terminal hypertrophic chondrocytes in an in vitro model of endochondral ossification. J Pathol 2003;201:496–503.
CrossRef Google scholar
[100]
RoachHI, Erenpreisa J, AignerT. Osteogenic differentiation of hypertrophic chondrocytes involves asymmetric cell divisions and apoptosis. J Cell Biol 1995;131:483–94.
CrossRef Google scholar
[101]
ParkJ, Gebhardt M, GolovchenkoS, et al. Dual pathways to endochondral osteoblasts: a novel chondrocyte-derived osteoprogenitor cell identified in hypertrophic cartilage. Biol Open 2015;4:608–21.
CrossRef Google scholar
[102]
TsangKY, ChanD, CheahKS. Fate of growth plate hypertrophic chondrocytes: death or lineage extension? Dev Growth Differ 2015;57:179–92.
CrossRef Google scholar
[103]
ChanCK, SeoEY, ChenJY, et al. Identification and specification of the mouse skeletal stem cell. Cell 2015;160:285–98.
CrossRef Google scholar
[104]
ChanCKF, GulatiGS, SinhaR, et al. Identification of the human skeletal stem cell. Cell 2018;175:43–56.e21.
CrossRef Google scholar
[105]
MizuhashiK, OnoW, MatsushitaY, et al. Resting zone of the growth plate houses a unique class of skeletal stem cells. Nature 2018;563:254–8.
CrossRef Google scholar
[106]
MuruganandanS, PierceR, TeguhDA, et al. A FoxA2+ long-term stem cell population is necessary for growth plate cartilage regeneration after injury. Nat Commun 2022;13:2515.
CrossRef Google scholar
[107]
KronenbergHM. The role of the perichondrium in fetal bone development. Ann N Y Acad Sci 2007;1116:59–64.
CrossRef Google scholar
[108]
KarlssonC, Thornemo M, HenrikssonHB, et al. Identification of a stem cell niche in the zone of ranvier within the knee joint. J Anat 2009;215:355–63.
CrossRef Google scholar
[109]
ShiY, HeG, LeeW-C, et al. Gli1 identifies osteogenic progenitors for bone formation and fracture repair. Nat Commun 2017;8:2043.
CrossRef Google scholar
[110]
PineaultKM, SongJY, KozloffKM, et al. Hox11 expressing regional skeletal stem cells are progenitors for osteoblasts, chondrocytes and adipocytes throughout life. Nat Commun 2019;10:3168.
CrossRef Google scholar
[111]
ChangH, Knothe Tate ML. Concise review: the periosteum: tapping into a reservoir of clinically useful progenitor cells. Stem Cells Transl Med 2012;1:480–91.
CrossRef Google scholar
[112]
MatthewsBG, Grcevic D, WangL, et al. Analysis of alphaSMA-labeled progenitor cell commitment identifies notch signaling as an important pathway in fracture healing. J Bone Miner Res 2014;29:1283–94.
CrossRef Google scholar
[113]
OrtinauLC, WangH, LeiK, et al. Identification of functionally distinct Mx1+alphaSMA+ periosteal skeletal stem cells. Cell Stem Cell 2019;25:784–96.e5.
CrossRef Google scholar
[114]
MatthewsBG et al. Heterogeneity of murine periosteum progenitors involved in fracture healing. Elife 2021;10:e58534.
CrossRef Google scholar
[115]
HeX, Bougioukli S, OrtegaB, et al. Sox9 positive periosteal cells in fracture repair of the adult mammalian long bone. Bone 2017;103:12–19.
CrossRef Google scholar
[116]
KuwaharaST et al. Sox9+ messenger cells orchestrate large-scale skeletal regeneration in the mammalian rib. Elife 2019;8:e40715.
CrossRef Google scholar
[117]
Duchamp de LagenesteO, Julien A, Abou-KhalilR, et al. Periosteum contains skeletal stem cells with high bone regenerative potential controlled by periostin. Nat Commun 2018;9:773.
CrossRef Google scholar
[118]
CostaAG, CusanoNE, SilvaBC, et al. Cathepsin k: its skeletal actions and role as a therapeutic target in osteoporosis. Nat Rev Rheumatol 2011;7:447–56.
CrossRef Google scholar
[119]
WhiteHE, Goswami A, TuckerAS. The intertwined evolution and development of sutures and cranial morphology. Front Cell Dev Biol 2021;9:653579.
CrossRef Google scholar
[120]
LentonKA, Nacamuli RP, WanDC, et al. Cranial suture biology. Curr Top Dev Biol 2005;66:287–328.
CrossRef Google scholar
[121]
OppermanLA. Cranial sutures as intramembranous bone growth sites. Dev Dyn 2000;219:472–85.
CrossRef Google scholar
[122]
HooperJE, ScottMP. Communicating with hedgehogs. Nat Rev Mol Cell Biol 2005;6:306–17.
CrossRef Google scholar
[123]
ZhaoH, FengJ, HoT-V, et al. The suture provides a niche for mesenchymal stem cells of craniofacial bones. Nat Cell Biol 2015;17:386–96.
CrossRef Google scholar
[124]
MartinJF, OlsonEN. Identification of a prx1 limb enhancer. Genesis 2000;26:225–9.
CrossRef Google scholar
[125]
WilkK, YehSA, MortensenLJ, et al. Postnatal calvarial skeletal stem cells expressing prx1 reside exclusively in the calvarial sutures and are required for bone regeneration. Stem Cell Rep 2017;8:933–46.
CrossRef Google scholar
[126]
ParkD, Spencer JA, KohBI, et al. Endogenous bone marrow mscs are dynamic, fate-restricted participants in bone maintenance and regeneration. Cell Stem Cell 2012;10:259–72.
CrossRef Google scholar
[127]
WorthleyDL, Churchill M, ComptonJT, et al. Gremlin 1 identifies a skeletal stem cell with bone, cartilage, and reticular stromal potential. Cell 2015;160:269–84.
CrossRef Google scholar
[128]
MatsushitaY, NagataM, KozloffKM, et al. A wnt-mediated transformation of the bone marrow stromal cell identity orchestrates skeletal regeneration. Nat Commun 2020;11:332.
CrossRef Google scholar
[129]
KawanamiA, Matsushita T, ChanYY, et al. Mice expressing gfp and creer in osteochondro progenitor cells in the periosteum. Biochem Biophys Res Commun 2009;386:477–82.
CrossRef Google scholar

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