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Journal of Orthopaedic Research :... Jan 2019The biology of bone healing is a rapidly developing science. Advances in transgenic and gene-targeted mice have enabled tissue and cell-specific investigations of... (Review)
Review
The biology of bone healing is a rapidly developing science. Advances in transgenic and gene-targeted mice have enabled tissue and cell-specific investigations of skeletal regeneration. As an example, only recently has it been recognized that chondrocytes convert to osteoblasts during healing bone, and only several years prior, seminal publications reported definitively that the primary tissues contributing bone forming cells during regeneration were the periosteum and endosteum. While genetically modified animals offer incredible insights into the temporal and spatial importance of various gene products, the complexity and rapidity of healing-coupled with the heterogeneity of animal models-renders studies of regenerative biology challenging. Herein, cells that play a key role in bone healing will be reviewed and extracellular mediators regulating their behavior discussed. We will focus on recent studies that explore novel roles of inflammation in bone healing, and the origins and fates of various cells in the fracture environment. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.
Topics: Animals; Bony Callus; Chondrocytes; Endothelial Progenitor Cells; Fracture Healing; Humans; Mesenchymal Stem Cells; Neovascularization, Physiologic; Osteoblasts; Osteoclasts; Osteogenesis; Signal Transduction
PubMed: 30370699
DOI: 10.1002/jor.24170 -
Endocrine Reviews Nov 2022More than 2.1 million age-related fractures occur in the United States annually, resulting in an immense socioeconomic burden. Importantly, the age-related deterioration... (Review)
Review
More than 2.1 million age-related fractures occur in the United States annually, resulting in an immense socioeconomic burden. Importantly, the age-related deterioration of bone structure is associated with impaired bone healing. Fracture healing is a dynamic process which can be divided into four stages. While the initial hematoma generates an inflammatory environment in which mesenchymal stem cells and macrophages orchestrate the framework for repair, angiogenesis and cartilage formation mark the second healing period. In the central region, endochondral ossification favors soft callus development while next to the fractured bony ends, intramembranous ossification directly forms woven bone. The third stage is characterized by removal and calcification of the endochondral cartilage. Finally, the chronic remodeling phase concludes the healing process. Impaired fracture healing due to aging is related to detrimental changes at the cellular level. Macrophages, osteocytes, and chondrocytes express markers of senescence, leading to reduced self-renewal and proliferative capacity. A prolonged phase of "inflammaging" results in an extended remodeling phase, characterized by a senescent microenvironment and deteriorating healing capacity. Although there is evidence that in the setting of injury, at least in some tissues, senescent cells may play a beneficial role in facilitating tissue repair, recent data demonstrate that clearing senescent cells enhances fracture repair. In this review, we summarize the physiological as well as pathological processes during fracture healing in endocrine disease and aging in order to establish a broad understanding of the biomechanical as well as molecular mechanisms involved in bone repair.
Topics: Humans; Fracture Healing; Bony Callus; Osteogenesis; Fractures, Bone; Cellular Senescence; Aging; Endocrine System Diseases
PubMed: 35182420
DOI: 10.1210/endrev/bnac008 -
International Journal of Biological... 2022The biomechanical environment plays a dominant role in fracture healing, and Piezo1 is regarded as a major mechanosensor in bone homeostasis. However, the role of Piezo1...
The biomechanical environment plays a dominant role in fracture healing, and Piezo1 is regarded as a major mechanosensor in bone homeostasis. However, the role of Piezo1 in fracture healing is not yet well characterized. In this study, we first delineated that Piezo1 is highly expressed in periosteal stem cells (PSCs) and their derived osteoblastic lineage cells and chondrocytes. Furthermore, downregulation of Piezo1 in callus leads to impaired fracture healing, while activation by its specific agonist promotes fracture healing through stimulation of PSC-modulated chondrogenesis and osteogenesis, along with accelerated cartilage-to-bone transformation. Interestingly, vascular endothelial growth factor A is upregulated after Yoda1 treatment of PSCs, indicating an indirect role of Piezo1 in angiogenesis. Mechanistically, activation of Piezo1 promotes expression of Yes-associated protein (YAP) and its nuclear localization in PSCs, which in turn increases the expression and nuclear localization of β-catenin. In detail, YAP directly interacts with β-catenin in the nucleus and forms a transcriptional YAP/β-catenin complex, which upregulates osteogenic, chondrogenic and angiogenic factors. Lastly, Yoda1 treatment significantly improves fracture healing in a delayed union mouse model generated by tail suspension. These findings indicate that Piezo1 is a potential therapeutic target for fracture delayed union or nonunion.
Topics: Animals; Bony Callus; Fracture Healing; Ion Channels; Mice; Osteogenesis; Stem Cells; Vascular Endothelial Growth Factor A; beta Catenin
PubMed: 35844802
DOI: 10.7150/ijbs.71390 -
Injury Jun 2021
Topics: Biomechanical Phenomena; Bony Callus; Fracture Healing; Humans
PubMed: 34099104
DOI: 10.1016/j.injury.2021.05.023 -
BMC Musculoskeletal Disorders May 2022The manual monitoring of callus with digital radiography (X-ray) is the primary bone healing evaluation, assessing the number of bridged callus formations. However, this... (Review)
Review
The manual monitoring of callus with digital radiography (X-ray) is the primary bone healing evaluation, assessing the number of bridged callus formations. However, this method is subjective and nonquantitative. Recently, several quantitative monitoring methods, which could assess the recovery of the structure and biomechanical properties of the callus at different stages and the process of bone healing, have been extensively investigated. These methods could reflect the bone mineral content (BMC), bone mineral density (BMD), stiffness, callus and bone metabolism at the site of bone lengthening. In this review, we comprehensively summarized the latest techniques for evaluating bone healing during distraction osteogenesis (DO): 1) digital radiography; 2) dual-energy X-ray scanning; 3) ultrasound; 4) quantitative computed tomography; 5) biomechanical evaluation; and 6) biochemical markers. This evidence will provide novel and significant information for evaluating bone healing during DO in the future.
Topics: Bone Density; Bony Callus; Humans; Osteogenesis; Osteogenesis, Distraction; Tibia; Tomography, X-Ray Computed
PubMed: 35610718
DOI: 10.1186/s12891-022-05458-8 -
Journal of Orthopaedic Research :... May 2015Type III collagen (Col3) has been proposed to play a key role in tissue repair based upon its temporospatial expression during the healing process of many tissues,...
Type III collagen (Col3) has been proposed to play a key role in tissue repair based upon its temporospatial expression during the healing process of many tissues, including bone. Given our previous finding that Col3 regulates the quality of cutaneous repair, as well as our recent data supporting its role in regulating osteoblast differentiation and trabecular bone quantity, we hypothesized that mice with diminished Col3 expression would exhibit altered long-bone fracture healing. To determine the role of Col3 in bone repair, young adult wild-type (Col3+/+) and haploinsufficent (Col3+/-) mice underwent bilateral tibial fractures. Healing was assessed 7, 14, 21, and 28 days following fracture utilizing microcomputed tomography (microCT), immunohistochemistry, and histomorphometry. MicroCT analysis revealed a small but significant increase in bone volume fraction in Col3+/- mice at day 21. However, histological analysis revealed that Col3+/- mice have less bone within the callus at days 21 and 28, which is consistent with the established role for Col3 in osteogenesis. Finally, a reduction in fracture callus osteoclastic activity in Col3+/- mice suggests Col3 also modulates callus remodeling. Although Col3 haploinsufficiency affected biological aspects of bone repair, it did not affect the regain of mechanical function in the young mice that were evaluated in this study. These findings provide evidence for a modulatory role for Col3 in fracture repair and support further investigations into its role in impaired bone healing.
Topics: Animals; Bone Regeneration; Bony Callus; Cell Proliferation; Collagen Type III; Female; Fracture Healing; Mice; Osteoclasts; Tibial Fractures; X-Ray Microtomography
PubMed: 25626998
DOI: 10.1002/jor.22838 -
Journal of Orthopaedic Science :... Mar 2012
Topics: Bone and Bones; Bony Callus; Electric Impedance; Electricity; History, 18th Century; History, 19th Century; History, 20th Century; History, Ancient; Humans; Japan; Orthopedics
PubMed: 22422052
DOI: 10.1007/s00776-012-0219-7 -
Canadian Medical Association Journal Aug 1963Recent studies on the epidemiology and repair of fractures are reviewed. The type and severity of the fracture bears a relation to the age, sex and occupation of the...
Recent studies on the epidemiology and repair of fractures are reviewed. The type and severity of the fracture bears a relation to the age, sex and occupation of the patient. Bone tissue after fracture shows a process of inflammation and repair common to all members of the connective tissue family, but it repairs with specific tissue. Cartilage forms when the oxygen supply is outgrown. After a fracture, the vascular bed enlarges. The major blood supply to healing tissue is from medullary vessels and destruction of them will cause necrosis of the inner two-thirds of the cortex. Callus rapidly mineralizes, but full mineralization is achieved slowly; increased mineral metabolism lasts several years after fracture.
Topics: Bone and Bones; Bony Callus; Cartilage; Fractures, Bone; Humans; Male; Wound Healing
PubMed: 13952119
DOI: No ID Found -
Current Osteoporosis Reports Apr 2018Bone fracture healing is a complex physiological process relying on numerous cell types and signals. Inflammatory factors secreted by immune cells help to control... (Review)
Review
PURPOSE OF REVIEW
Bone fracture healing is a complex physiological process relying on numerous cell types and signals. Inflammatory factors secreted by immune cells help to control recruitment, proliferation, differentiation, and activation of hematopoietic and mesenchymal cells. Within this review we will discuss the functional role of immune cells as it pertains to bone fracture healing. In doing so, we will outline the cytokines secreted and their effects within the healing fracture callus.
RECENT FINDINGS
Macrophages have been found to play an important role in fracture healing. These immune cells signal to other cells of the fracture callus, modulating bone healing. Cytokines and cellular signals within fracture healing continue to be studied. The findings from this work have helped to reinforce the importance of osteoimmunity in bone fracture healing. Owing to these efforts, immunomodulation is emerging as a potential therapeutic target to improve bone fracture healing.
Topics: Bony Callus; Cell Differentiation; Cell Proliferation; Cytokines; Fracture Healing; Hematopoietic Stem Cells; Humans; Macrophages; Mesenchymal Stem Cells
PubMed: 29508143
DOI: 10.1007/s11914-018-0423-2 -
European Cells & Materials Jun 2021The present review acknowledges the tremendous impact of Stephan Perren's strain theory, considered with respect to the earlier contributions of Roux and Pauwels. Then,... (Review)
Review
The present review acknowledges the tremendous impact of Stephan Perren's strain theory, considered with respect to the earlier contributions of Roux and Pauwels. Then, it provides further insight by examining how the concept of reverse dynamisation extended Perren's theory within a modern context. A key factor of this more contemporary theory is that it introduces variable mechanical conditions at different time points during bone healing, opening the possibility of manipulating biology through mechanics to achieve the desired clinical outcome. The discussion focusses on the current state of the art and the most recent advances made towards optimising and accelerating bone regeneration, by actively controlling the mechanical environment as healing progresses. Reverse dynamisation utilises a very specific mechanical manipulation regimen, with conditions initially flexible to encourage and expedite early callus formation. Once callus has formed, the mechanical conditions are intentionally modified to create a rigid environment under which the soft callus is quickly converted to hard callus, bridging the fracture site and leading to a more rapid union. The relevant literature, principally animal studies, was surveyed to provide ample evidence in support of the effectiveness of reverse dynamisation. By providing a modern perspective on Stephan Perren's strain theory, reverse dynamisation perhaps holds the key to tipping the balance in favour of a more rapid and reliable union when treating acute fractures, osteotomies, non-unions and other circumstances where it is necessary to regenerate bone.
Topics: Animals; Bone Regeneration; Bone and Bones; Bony Callus; Fracture Healing; Fractures, Bone; Humans
PubMed: 34111297
DOI: 10.22203/eCM.v041a43