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Annals of the Rheumatic Diseases Dec 2020Osteophytes are highly prevalent in osteoarthritis (OA) and are associated with pain and functional disability. These pathological outgrowths of cartilage and bone...
OBJECTIVES
Osteophytes are highly prevalent in osteoarthritis (OA) and are associated with pain and functional disability. These pathological outgrowths of cartilage and bone typically form at the junction of articular cartilage, periosteum and synovium. The aim of this study was to identify the cells forming osteophytes in OA.
METHODS
Fluorescent genetic cell-labelling and tracing mouse models were induced with tamoxifen to switch on reporter expression, as appropriate, followed by surgery to induce destabilisation of the medial meniscus. Contributions of fluorescently labelled cells to osteophytes after 2 or 8 weeks, and their molecular identity, were analysed by histology, immunofluorescence staining and RNA in situ hybridisation. mice and mice crossed with multicolour reporter mice were used for identification and clonal tracing of mesenchymal progenitors. Mice carrying , , , , or were crossed with tdTomato reporter mice to lineage-trace chondrocytes and stem/progenitor cell subpopulations.
RESULTS
Articular chondrocytes, or skeletal stem cells identified by , or expression, did not give rise to osteophytes. Instead, osteophytes derived from -expressing stem/progenitor cells in periosteum and synovium that are descendants from the -expressing embryonic joint interzone. Further, we show that -expressing progenitors in periosteum supplied hybrid skeletal cells to the early osteophyte, while -expressing progenitors from synovial lining contributed to cartilage capping the osteophyte, but not to bone.
CONCLUSION
Our findings reveal distinct periosteal and synovial skeletal progenitors that cooperate to form osteophytes in OA. These cell populations could be targeted in disease modification for treatment of OA.
Topics: Animals; Cell Lineage; Mice; Osteoarthritis; Osteophyte; Periosteum; Stem Cells; Synovial Membrane
PubMed: 32963046
DOI: 10.1136/annrheumdis-2020-218350 -
Cell Stem Cell Nov 2022A fundamental question in bone biology concerns the contributions of skeletal stem/progenitor cells (SSCs) in the bone marrow versus the periosteum to bone repair. We...
A fundamental question in bone biology concerns the contributions of skeletal stem/progenitor cells (SSCs) in the bone marrow versus the periosteum to bone repair. We found that SSCs in adult bone marrow can be identified based on Lepr and Adiponectin-cre/creER expression while SSCs in adult periosteum can be identified based on Gli1 expression. Under steady-state conditions, new bone arose primarily from bone marrow SSCs. After bone injuries, both SSC populations began proliferating but made very different contributions to bone repair. Drill injuries were primarily repaired by LepR/Adiponectin bone marrow SSCs. Conversely, bicortical fractures were primarily repaired by Gli1 periosteal SSCs, though LepR/Adiponectin bone marrow cells transiently formed trabecular bone at the fracture site. Gli1 periosteal cells also regenerated LepR bone marrow stromal cells that expressed hematopoietic niche factors at fracture sites. Different bone injuries are thus repaired by different SSCs, with periosteal cells regenerating bone and marrow stroma after non-stabilized fractures.
Topics: Humans; Adult; Bone Marrow; Zinc Finger Protein GLI1; Adiponectin; Stem Cells; Periosteum; Bone Marrow Cells
PubMed: 36272401
DOI: 10.1016/j.stem.2022.10.002 -
Romanian Journal of Morphology and... 2016Fracture healing is a complex process that involves presence of osteoprogenitor cells and growth factors. Therefore, the integrity of the fracture site surrounding... (Review)
Review
Fracture healing is a complex process that involves presence of osteoprogenitor cells and growth factors. Therefore, the integrity of the fracture site surrounding tissues including periosteum is necessary in order to provide the resources for bone regeneration. The purpose of this review is to organize and synthesize the relevant information regarding periosteum and fracture repair. Periosteum cells are involved in endochondral or intramembranous ossification according to the presence of a new formed cartilage. The periosteal osteoprogenitor mesenchymal cells differentiation is guided by a multitude of signaling molecules, especially bone morphogenetic protein 2 (BMP2), but also as a response to mechanical stimuli. If the periosteum is traumatized or removed, there are other osteoprogenitor cell sources as the ones located in the medullar cavity of the bones, the pericytes from the blood vessel walls as well as the undifferentiated cells from the adjacent soft tissue, muscles and fascia. However, total absence of the periosteum and lesions of the intramedullary vascular network is associated with fracture non-union. In these cases, muscular tissue surrounding the site could take over some of the cambium functions. In conclusion, there are other factors that can influence significantly fracture healing, besides periosteum.
Topics: Bone Morphogenetic Protein 2; Fracture Healing; Humans; Periosteum
PubMed: 28174786
DOI: No ID Found -
Current Osteoporosis Reports Apr 2022Periosteal apposition and endosteal remodeling regulate cortical bone expansion and thickness, both critical determinants of bone strength. Yet, the cellular... (Review)
Review
PURPOSE OF REVIEW
Periosteal apposition and endosteal remodeling regulate cortical bone expansion and thickness, both critical determinants of bone strength. Yet, the cellular characteristics and local or paracrine factors that regulate the periosteum and endosteum remain largely elusive. Here we discuss novel insights in cortical bone growth, expansion, and homeostasis, provided by the study of Secreted Frizzled Receptor Protein 4 (Sfrp4), a decoy receptor for Wnt ligands.
RECENT FINDINGS
SFRP4 loss-of function mutations cause Pyle disease, a rare skeletal disorder characterized by cortical bone thinning and increased fragility fractures despite increased trabecular bone density. On the endosteal surface, Sfrp4-mediated repression of non-canonical Wnt signaling regulates endosteal resorption. On the periosteum, Sfrp4 identifies as a critical functional mediator of periosteal stem cell/progenitor expansion and differentiation. Analysis of signaling pathways regulating skeletal stem cells/progenitors provides an opportunity to advance our understanding of the mechanisms involved in cortical bone biology.
Topics: Biology; Cell Differentiation; Cortical Bone; Frizzled Receptors; Humans; Periosteum; Proto-Oncogene Proteins
PubMed: 35182301
DOI: 10.1007/s11914-022-00727-w -
Journal of Bone and Mineral Research :... Aug 2022Bone regeneration involves skeletal stem/progenitor cells (SSPCs) recruited from bone marrow, periosteum, and adjacent skeletal muscle. To achieve bone reconstitution...
Bone regeneration involves skeletal stem/progenitor cells (SSPCs) recruited from bone marrow, periosteum, and adjacent skeletal muscle. To achieve bone reconstitution after injury, a coordinated cellular and molecular response is required from these cell populations. Here, we show that SSPCs from periosteum and skeletal muscle are enriched in osteochondral progenitors, and more efficiently contribute to endochondral ossification during fracture repair as compared to bone-marrow stromal cells. Single-cell RNA sequencing (RNAseq) analyses of periosteal cells reveal the cellular heterogeneity of periosteum at steady state and in response to bone fracture. Upon fracture, both periosteal and skeletal muscle SSPCs transition from a stem/progenitor to a fibrogenic state prior to chondrogenesis. This common activation pattern in periosteum and skeletal muscle SSPCs is mediated by bone morphogenetic protein (BMP) signaling. Functionally, Bmpr1a gene inactivation in platelet-derived growth factor receptor alpha (Pdgfra)-derived SSPCs impairs bone healing and decreases SSPC proliferation, migration, and osteochondral differentiation. These results uncover a coordinated molecular program driving SSPC activation in periosteum and skeletal muscle toward endochondral ossification during bone regeneration. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Topics: Cell Differentiation; Chondrogenesis; Fractures, Bone; Humans; Muscle, Skeletal; Osteogenesis; Periosteum; Stem Cells
PubMed: 35652423
DOI: 10.1002/jbmr.4616 -
Orthopaedic Surgery Sep 2022Repairing large segment bone defects is still a clinical challenge. Bone tissue prefabrication shows great translational potentials and has been gradually accepted... (Review)
Review
Repairing large segment bone defects is still a clinical challenge. Bone tissue prefabrication shows great translational potentials and has been gradually accepted clinically. Existing bone reconstruction strategies, including autologous periosteal graft, allogeneic periosteal transplantation, xenogeneic periosteal transplantation, and periosteal cell tissue engineering, are all clinically valuable treatments and have made significant progress in research. Herein, we reviewed the research progress of these techniques and briefly explained the relationship among in vivo microenvironment, mechanical force, and periosteum osteogenesis. Moreover, we also highlighted the importance of the critical role of periosteum in osteogenesis and explained current challenges and future perspective.
Topics: Autografts; Bioreactors; Humans; Osteogenesis; Periosteum; Tissue Engineering
PubMed: 35794789
DOI: 10.1111/os.13325 -
Cell Stem Cell Dec 2019The periosteum is critical for bone maintenance and healing. However, the in vivo identity and specific regulatory mechanisms of adult periosteum-resident skeletal stem...
The periosteum is critical for bone maintenance and healing. However, the in vivo identity and specific regulatory mechanisms of adult periosteum-resident skeletal stem cells are unknown. Here, we report animal models that selectively and durably label postnatal Mx1+αSMA+ periosteal stem cells (P-SSCs) and establish that P-SSCs are a long-term repopulating, functionally distinct SSC subset responsible for lifelong generation of periosteal osteoblasts. P-SSCs rapidly migrate toward an injury site, supply osteoblasts and chondrocytes, and recover new periosteum. Notably, P-SSCs specifically express CCL5 receptors, CCR3 and CCR5. Real-time intravital imaging revealed that the treatment with CCL5 induces P-SSC migration in vivo and bone healing, while CCL5/CCR5 deletion, CCR5 inhibition, or local P-SSC ablation reduces osteoblast number and delays bone healing. Human periosteal cells express CCR5 and undergo CCL5-mediated migration. Thus, the adult periosteum maintains genetically distinct SSC subsets with a CCL5-dependent migratory mechanism required for bone maintenance and injury repair.
Topics: Actins; Adolescent; Adult; Animals; Cell Movement; Child; Female; Flow Cytometry; Fluorescent Antibody Technique; Humans; Immunohistochemistry; Male; Mice, Inbred C57BL; Microarray Analysis; Myxovirus Resistance Proteins; Periosteum; Reverse Transcriptase Polymerase Chain Reaction; Stem Cells; Young Adult
PubMed: 31809737
DOI: 10.1016/j.stem.2019.11.003 -
Biology Direct Oct 2021Periosteum is a thin membrane covering bone surfaces and consists of two layers: outer fibrous layer and inner cambium layer. Simple appearance of periosteum has belied... (Review)
Review
Periosteum is a thin membrane covering bone surfaces and consists of two layers: outer fibrous layer and inner cambium layer. Simple appearance of periosteum has belied its own complexity as a composite structure for physical bone protection, mechano-sensor for sensing mechanical loading, reservoir of biochemical molecules for initiating cascade signaling, niche of osteogenic cells for bone formation and repair, and "umbilical cord" for nourishing bone tissue. Periosteum-derived cells (PDCs) have stem cell attributes: self-renewal (no signs of senescence until 80 population doublings) and multipotency (differentiate into fibroblasts, osteoblasts, chondrocytes, adipocytes and skeletal myocytes). In this review, we summarized the currently available knowledge about periosteum and with special references to antler-lineage periostea, and demonstrated that although periosteum is a type of simple tissue in appearance, with multiple faces in functions; antler-lineage periostea add another dimension to the properties of somatic periostea: capable of initiation of ectopic organ formation upon transplantation and full mammalian organ regeneration when interacted with the covering skin. Very recently, we have translated this finding into other mammals, i.e. successfully induced partial regeneration of the amputated rat legs. We believe further refinement along this line would greatly benefit human health.
Topics: Animals; Antlers; Deer; Osteogenesis; Periosteum; Rats; Stem Cells
PubMed: 34663443
DOI: 10.1186/s13062-021-00310-w -
Journal of Dental Research Feb 2014The bone-regenerative potentials of the periosteum have been explored as early as the 17th century. Over the past few years, however, much has been discovered in terms... (Review)
Review
The bone-regenerative potentials of the periosteum have been explored as early as the 17th century. Over the past few years, however, much has been discovered in terms of the molecular and cellular mechanisms that control the periosteal contribution to bone regeneration. Lineage tracing analyses and knock-in transgenic mice have helped define the relative contributions of the periosteum and endosteum to bone regeneration. Additional studies have shed light on the critical roles that BMP, FGF, Hedgehog, Notch, PDGF, Wnt, and inflammation signaling have or may have in periosteal-mediated bone regeneration, fostering the path to novel approaches in bone-regenerative therapy. Thus, by examining the role that each pathway has in periosteal-mediated bone regeneration, in this review we analyze the status of the current research on the regenerative potential of the periosteum. The provided analysis aims to inform both clinician-scientists who may have interest in the current studies about the biology of the periosteum as well as dental surgeons who may find this review useful to perform periosteal-harnessing bone-regenerative procedures.
Topics: Animals; Biology; Bone Regeneration; Cell Lineage; Facial Bones; Humans; Intercellular Signaling Peptides and Proteins; Periosteum; Signal Transduction; Skull; Tissue Engineering
PubMed: 24088412
DOI: 10.1177/0022034513506445 -
Bone Feb 2021Diabetics are at increased risk for fracture, and experience severely impaired skeletal healing characterized by delayed union or nonunion of the bone. The periosteum...
Diabetics are at increased risk for fracture, and experience severely impaired skeletal healing characterized by delayed union or nonunion of the bone. The periosteum harbors osteochondral progenitors that can differentiate into chondrocytes and osteoblasts, and this connective tissue layer is required for efficient fracture healing. While bone marrow-derived stromal cells have been studied extensively in the context of diabetic skeletal repair and osteogenesis, the effect of diabetes on the periosteum and its ability to contribute to bone regeneration has not yet been explicitly evaluated. Within this study, we utilized an established murine model of type I diabetes to evaluate periosteal cell differentiation capacity, proliferation, and availability under the effect of a diabetic environment. Periosteal cells from diabetic mice were deficient in osteogenic differentiation ability in vitro, and diabetic mice had reduced periosteal populations of mesenchymal progenitors with a corresponding reduction in proliferation capacity following injury. Additionally, fracture callus mineralization and mature osteoblast activity during periosteum-mediated healing was impaired in diabetic mice compared to controls. We propose that the effect of diabetes on periosteal progenitors and their ability to aid in skeletal repair directly impairs fracture healing.
Topics: Animals; Bony Callus; Cell Differentiation; Diabetes Mellitus, Experimental; Fracture Healing; Mice; Osteogenesis; Periosteum
PubMed: 33221502
DOI: 10.1016/j.bone.2020.115764