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Journal of Orthopaedic Translation Mar 2022Periosteum plays a significant role in bone formation and regeneration by storing progenitor cells, and also acts as a source of local growth factors and a scaffold for... (Review)
Review
BACKGROUND
Periosteum plays a significant role in bone formation and regeneration by storing progenitor cells, and also acts as a source of local growth factors and a scaffold for recruiting cells and other growth factors. Recently, tissue-engineered periosteum has been studied extensively and shown to be important for osteogenesis and chondrogenesis. Using biomimetic methods for artificial periosteum synthesis, membranous tissues with similar function and structure to native periosteum are produced that significantly improve the efficacy of bone grafting and scaffold engineering, and can serve as direct replacements for native periosteum. Many problems involving bone defects can be solved by preparation of idealized periosteum from materials with different properties using various techniques.
METHODS
This review summarizes the significance of periosteum for osteogenesis and chondrogenesis from the aspects of periosteum tissue structure, osteogenesis performance, clinical application, and development of periosteum tissue engineering. The advantages and disadvantages of different tissue engineering methods are also summarized.
RESULTS
The fast-developing field of periosteum tissue engineering is aimed toward synthesis of bionic periosteum that can ensure or accelerate the repair of bone defects. Artificial periosteum materials can be similar to natural periosteum in both structure and function, and have good therapeutic potential. Induction of periosteum tissue regeneration and bone regeneration by biomimetic periosteum is the ideal process for bone repair.
CONCLUSIONS
Periosteum is essential for bone formation and regeneration, and it is indispensable in bone repair. Achieving personalized structure and composition in the construction of tissue engineering periosteum is in accordance with the design concept of both universality and emphasis on individual differences and ensures the combination of commonness and individuality, which are expected to meet the clinical needs of bone repair more effectively.
THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE
To better understand the role of periosteum in bone repair, clarify the present research situation of periosteum and tissue engineering periosteum, and determine the development and optimization direction of tissue engineering periosteum in the future. It is hoped that periosteum tissue engineering will play a greater role in meeting the clinical needs of bone repair in the future, and makes it possible to achieve optimization of bone tissue therapy.
PubMed: 35228996
DOI: 10.1016/j.jot.2022.01.002 -
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 -
Nature Oct 2018Bone consists of separate inner endosteal and outer periosteal compartments, each with distinct contributions to bone physiology and each maintaining separate pools of...
Bone consists of separate inner endosteal and outer periosteal compartments, each with distinct contributions to bone physiology and each maintaining separate pools of cells owing to physical separation by the bone cortex. The skeletal stem cell that gives rise to endosteal osteoblasts has been extensively studied; however, the identity of periosteal stem cells remains unclear. Here we identify a periosteal stem cell (PSC) that is present in the long bones and calvarium of mice, displays clonal multipotency and self-renewal, and sits at the apex of a differentiation hierarchy. Single-cell and bulk transcriptional profiling show that PSCs display transcriptional signatures that are distinct from those of other skeletal stem cells and mature mesenchymal cells. Whereas other skeletal stem cells form bone via an initial cartilage template using the endochondral pathway, PSCs form bone via a direct intramembranous route, providing a cellular basis for the divergence between intramembranous versus endochondral developmental pathways. However, there is plasticity in this division, as PSCs acquire endochondral bone formation capacity in response to injury. Genetic blockade of the ability of PSCs to give rise to bone-forming osteoblasts results in selective impairments in cortical bone architecture and defects in fracture healing. A cell analogous to mouse PSCs is present in the human periosteum, raising the possibility that PSCs are attractive targets for drug and cellular therapy for skeletal disorders. The identification of PSCs provides evidence that bone contains multiple pools of stem cells, each with distinct physiologic functions.
Topics: Animals; Bone Development; Bone and Bones; Cathepsin K; Cell Differentiation; Female; Femur; Fracture Healing; Gene Expression Regulation; Humans; Male; Mesenchymal Stem Cells; Mice; Osteoblasts; Periosteum; Skull; Stem Cells
PubMed: 30250253
DOI: 10.1038/s41586-018-0554-8 -
The Journal of Clinical Investigation Dec 2019Bone is richly innervated by nerve growth factor-responsive (NGF-responsive) tropomyosin receptor kinase A-expressing (TrKa-expressing) sensory nerve fibers, which are...
Bone is richly innervated by nerve growth factor-responsive (NGF-responsive) tropomyosin receptor kinase A-expressing (TrKa-expressing) sensory nerve fibers, which are required for osteochondral progenitor expansion during mammalian skeletal development. Aside from pain sensation, little is known regarding the role of sensory innervation in bone repair. Here, we characterized the reinnervation of tissue following experimental ulnar stress fracture and assessed the impact of loss of TrkA signaling in this process. Sequential histological data obtained in reporter mice subjected to fracture demonstrated a marked upregulation of NGF expression in periosteal stromal progenitors and fracture-associated macrophages. Sprouting and arborization of CGRP+TrkA+ sensory nerve fibers within the reactive periosteum in NGF-enriched cellular domains were evident at time points preceding periosteal vascularization, ossification, and mineralization. Temporal inhibition of TrkA catalytic activity by administration of 1NMPP1 to TrkAF592A mice significantly reduced the numbers of sensory fibers, blunted revascularization, and delayed ossification of the fracture callus. We observed similar deficiencies in nerve regrowth and fracture healing in a mouse model of peripheral neuropathy induced by paclitaxel treatment. Together, our studies demonstrate an essential role of TrkA signaling for stress fracture repair and implicate skeletal sensory nerves as an important upstream mediator of this repair process.
Topics: Animals; Disease Models, Animal; Fracture Healing; Fractures, Bone; Fractures, Stress; Ganglia, Spinal; Genes, Reporter; Imaging, Three-Dimensional; Male; Mice; Mice, Inbred C57BL; Nerve Growth Factor; Osteogenesis; Periosteum; Receptor, trkA; Sensory Receptor Cells; Signal Transduction; Stem Cells; Transgenes; X-Ray Microtomography
PubMed: 31638597
DOI: 10.1172/JCI128428 -
Nature Medicine Oct 2016Orthopedic implants containing biodegradable magnesium have been used for fracture repair with considerable efficacy; however, the underlying mechanisms by which these...
Orthopedic implants containing biodegradable magnesium have been used for fracture repair with considerable efficacy; however, the underlying mechanisms by which these implants improve fracture healing remain elusive. Here we show the formation of abundant new bone at peripheral cortical sites after intramedullary implantation of a pin containing ultrapure magnesium into the intact distal femur in rats. This response was accompanied by substantial increases of neuronal calcitonin gene-related polypeptide-α (CGRP) in both the peripheral cortex of the femur and the ipsilateral dorsal root ganglia (DRG). Surgical removal of the periosteum, capsaicin denervation of sensory nerves or knockdown in vivo of the CGRP-receptor-encoding genes Calcrl or Ramp1 substantially reversed the magnesium-induced osteogenesis that we observed in this model. Overexpression of these genes, however, enhanced magnesium-induced osteogenesis. We further found that an elevation of extracellular magnesium induces magnesium transporter 1 (MAGT1)-dependent and transient receptor potential cation channel, subfamily M, member 7 (TRPM7)-dependent magnesium entry, as well as an increase in intracellular adenosine triphosphate (ATP) and the accumulation of terminal synaptic vesicles in isolated rat DRG neurons. In isolated rat periosteum-derived stem cells, CGRP induces CALCRL- and RAMP1-dependent activation of cAMP-responsive element binding protein 1 (CREB1) and SP7 (also known as osterix), and thus enhances osteogenic differentiation of these stem cells. Furthermore, we have developed an innovative, magnesium-containing intramedullary nail that facilitates femur fracture repair in rats with ovariectomy-induced osteoporosis. Taken together, these findings reveal a previously undefined role of magnesium in promoting CGRP-mediated osteogenic differentiation, which suggests the therapeutic potential of this ion in orthopedics.
Topics: Animals; Bone Nails; Calcitonin Gene-Related Peptide; Calcitonin Receptor-Like Protein; Capsaicin; Cation Transport Proteins; Cell Differentiation; Cyclic AMP Response Element-Binding Protein; Denervation; Female; Femoral Fractures; Femur; Fracture Fixation, Intramedullary; Fracture Healing; Ganglia, Spinal; Gene Knock-In Techniques; Gene Knockdown Techniques; Humans; Magnesium; Neurons; Osteogenesis; Osteoporosis, Postmenopausal; Osteoporotic Fractures; Ovariectomy; Periosteum; Rats; Receptor Activity-Modifying Protein 1; Sensory System Agents; Stem Cells; TRPM Cation Channels; Transcription Factors
PubMed: 27571347
DOI: 10.1038/nm.4162 -
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