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Aging Cell Jun 2023As we age, our bones undergo a process of loss, often accompanied by muscle weakness and reduced physical activity. This is exacerbated by decreased responsiveness to...
As we age, our bones undergo a process of loss, often accompanied by muscle weakness and reduced physical activity. This is exacerbated by decreased responsiveness to mechanical stimulation in aged skeleton, leading to the hypothesis that decreased mechanical stimulation plays an important role in age-related bone loss. Piezo1, a mechanosensitive ion channel, is critical for bone homeostasis and mechanotransduction. Here, we observed a decrease in Piezo1 expression with age in both murine and human cortical bone. Furthermore, loss of Piezo1 in osteoblasts and osteocytes resulted in an increase in age-associated cortical bone loss compared to control mice. The loss of cortical bone was due to an expansion of the endosteal perimeter resulting from increased endocortical resorption. In addition, expression of Tnfrsf11b, encoding anti-osteoclastogenic protein OPG, decreases with Piezo1 in vitro and in vivo in bone cells, suggesting that Piezo1 suppresses osteoclast formation by promoting Tnfrsf11b expression. Our results highlight the importance of Piezo1-mediated mechanical signaling in protecting against age-associated cortical bone loss by inhibiting bone resorption in mice.
Topics: Aged; Animals; Humans; Mice; Bone and Bones; Bone Diseases, Metabolic; Cortical Bone; Ion Channels; Mechanotransduction, Cellular; Osteoblasts; Osteoclasts
PubMed: 37147884
DOI: 10.1111/acel.13846 -
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 -
Tissue Engineering. Part B, Reviews Apr 2022Bone is composed of dense and solid cortical bone and honeycomb-like trabecular bone. Although cortical bone provides the majority of mechanical strength for a bone,... (Review)
Review
Bone is composed of dense and solid cortical bone and honeycomb-like trabecular bone. Although cortical bone provides the majority of mechanical strength for a bone, there are few studies focusing on cortical bone repair or regeneration. Osteons (the Haversian system) form structural and functional units of cortical bone. In recent years, emerging evidences have shown that the osteon structure (including osteocytes, lamellae, lacunocanalicular network, and Haversian canals) plays critical roles in bone mechanics and turnover. Therefore, reconstruction of the osteon structure is crucial for cortical bone regeneration. This article provides a systematic summary of recent advances in osteons, including the structure, function, turnover, and regenerative strategies. First, the hierarchical structure of osteons is illustrated and the critical functions of osteons in bone dynamics are introduced. Next, the modeling and remodeling processes of osteons at a cellular level and the turnover of osteons in response to mechanical loading and aging are emphasized. Furthermore, several bioengineering approaches that were recently developed to recapitulate the osteon structure are highlighted. Impact statement This review provides a comprehensive summary of recent advances in osteons, especially the roles in bone formation, remodeling, and regeneration. Besides introducing the hierarchical structure and critical functions of osteons, we elucidate the modeling and remodeling of osteons at a cellular level. Specifically, we highlight the bioengineering approaches that were recently developed to mimic the hierarchical structure of osteons. We expect that this review will provide informative insights and attract increasing attentions in orthopedic community, shedding light on cortical bone regeneration in the future.
Topics: Bone Regeneration; Bone and Bones; Haversian System; Humans; Osteocytes; Osteogenesis
PubMed: 33487116
DOI: 10.1089/ten.TEB.2020.0322 -
Bone Dec 2020The acquisition of a high bone density at a young age is a strategy to prevent fractures/falls later in life. We therefore decided to investigate the increases in... (Review)
Review
BACKGROUND
The acquisition of a high bone density at a young age is a strategy to prevent fractures/falls later in life. We therefore decided to investigate the increases in cortical thickness (CoTh) and trabecular bone density (TBD) of children.
METHODS
Subjects comprised 1314 students (678 boys and 636 girls) aged between 12 and 18 years. Lifestyle factors were examined with a self-administered questionnaire (sleep times, exercise habits, and calcium intake). Bone growth was assessed based on CoTh and TBD using an ultrasonic bone densitometer. Height, weight, and body fat percentage were also measured.
RESULTS
Increases in CoTh and TBD occurred earlier in girls than in boys. Calcium intake was not sufficient at any of the ages examined, and sleep times were shorter than those recommended by the National Sleep Foundation. Increases in CoTh and TBD occurred subsequent to increases in height. Although increases in CoTh were observed with age in both sexes, TBD increased in boys until the age of 17 years and in girls until the age of 15 years. At 18 years of age, the young adult mean value was greater than 100% for CoTh but lower than 100% for TBD. A multivariate analysis identified age, body mass index (BMI), and exercise as independent positive factors for CoTh, while body fat percentage was an independent negative factor. Age and BMI were independent positive factors for TBD in both sexes, whereas body fat percentage was a positive factor in boys only.
CONCLUSIONS
The study found that CoTH and TBD varied with age and differed in increase in boys and girls; related factors of bone increase could also be found. The results of this study may contribute to the acquisition of high bone density in children and adolescents.
Topics: Adolescent; Bone Density; Cancellous Bone; Child; Cortical Bone; Exercise; Female; Humans; Japan; Male; Young Adult
PubMed: 33022454
DOI: 10.1016/j.bone.2020.115669 -
Tissue Engineering and Regenerative... Jun 2021Although bone tissue engineering has already been applied clinically, its regeneration efficacy is not always sufficient. Local inflammatory cytokines are considered as...
BACKGROUND
Although bone tissue engineering has already been applied clinically, its regeneration efficacy is not always sufficient. Local inflammatory cytokines are considered as the major factors that induce apoptosis of transplanted cells, thus leading to insufficient new bone formation. In this study, we focused on the effects of interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-α) on differentiation and apoptosis of compact bone-derived cells (CBDCs).
METHODS
CBDCs were obtained from mouse legs and cultured. The effects of TNF-α and/or IL-6 on the osteogenic differentiation and apoptosis of CBDCs were analyzed in vitro. To confirm the expression of local inflammatory cytokines in vivo, CBDCs were transplanted to the back of immunocompetent mice.
RESULTS
IL-6 exerted inconsistent effects on the expression of the different osteogenic markers tested, while significantly upregulating Fas. By contrast, the addition of TNF-α dramatically reduced the expression of all tested osteogenic markers and increased Fas expression. The highest dose of IL-6 could partially reverse the repressive effect of TNF-α, while the addition of IL-6 further increased Fas expression in CBDCs compared to TNF-α alone. The results from in vivo experiments showed the presence of transplants with and without new bone formation. The transplants without bone formation were characterized by higher IL-6 and lower IL-10 expression than those with bone formation, while the expression of TNF-α did not show notable difference.
CONCLUSION
The results of this study suggest an important role for IL-6 in modulating the efficacy of bone tissue engineering, which can affect osteogenic cells both positively and negatively.
Topics: Animals; Cell Differentiation; Cortical Bone; Interleukin-6; Mice; Osteogenesis; Tumor Necrosis Factor-alpha
PubMed: 33847914
DOI: 10.1007/s13770-021-00336-1 -
Current Osteoporosis Reports Dec 2019Individuals with type 1 and type 2 diabetes mellitus (T1DM, T2DM) have an increased risk of bone fracture compared to non-diabetic controls that is not explained by... (Review)
Review
PURPOSE OF REVIEW
Individuals with type 1 and type 2 diabetes mellitus (T1DM, T2DM) have an increased risk of bone fracture compared to non-diabetic controls that is not explained by differences in BMD, BMI, or falls. Thus, bone tissue fracture resistance may be reduced in individuals with DM. The purpose of this review is to summarize work that analyzes the effects of T1DM and T2DM on bone tissue compositional and mechanical properties.
RECENT FINDINGS
Studies of clinical T2DM specimens revealed increased mineralization and advanced glycation endproduct (AGE) concentrations and significant relationships between mechanical performance and composition of cancellous bone. Specifically, in femoral cancellous tissue, compressive stiffness and strength increased with mineral content; and post-yield properties decreased with AGE concentration. In addition, cortical resistance to in vivo indentation (bone material strength index) was lower in patients with T2DM vs. age-matched non-diabetic controls, and this resistance decreased with worsening glycemic control. Recent studies on patients with T1DM and history of a prior fragility fracture found greater mineral content and concentrations of AGEs in iliac trabecular bone and correspondingly stiffer, harder bone at the nanosacle. Recent observational data showed greater AGE and mineral content in surgically retrieved bone from patients with T2DM vs. non-DM controls, consistent with reduced bone remodeling. Limited data on human T1DM bone tissue also showed higher mineral and AGE content in patients with prior fragility fractures compared to non-DM and non-fracture controls.
Topics: Animals; Biomechanical Phenomena; Blood Glucose; Bone Density; Bone Remodeling; Bone and Bones; Cancellous Bone; Cortical Bone; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Fractures, Bone; Glycation End Products, Advanced; Humans
PubMed: 31713179
DOI: 10.1007/s11914-019-00538-6 -
Journal of Orthopaedic Surgery and... May 2020What is the right surface for an implant to achieve biological fixation? Surface technologies can play important roles in encouraging interactions between the implant...
BACKGROUND
What is the right surface for an implant to achieve biological fixation? Surface technologies can play important roles in encouraging interactions between the implant surface and the host bone to achieve osseointegration. Preclinical animal models provide important insight into in vivo performance related to bone ongrowth and implant fixation.
METHODS
A large animal model was used to compare the in vivo response of HA and plasma-sprayed titanium coatings in a well-reported adult ovine model to evaluate bone ongrowth in terms of mechanical properties in cortical sites, and histology and histomorphometry in cortical and cancellous sites at 4 and 12 weeks.
RESULTS
Titanium plasma-sprayed surfaces outperformed the HA-coated samples in push-out testing in cortical sites while both surfaces supported new bone ongrowth and remodeling in cortical and cancellous sites.
CONCLUSIONS
While both HA and Ti plasma provided an osteoconductive surface for bone ongrowth, the Ti plasma provided a more robust bone-implant interface that ideally would be required for load transfer and implant stability in the longer term.
Topics: Animals; Biomechanical Phenomena; Bone Plates; Cancellous Bone; Cortical Bone; Shear Strength; Sheep; Titanium
PubMed: 32408885
DOI: 10.1186/s13018-020-01696-5 -
Osteoporosis International : a Journal... Jun 2019Liver cirrhosis leads to bone loss. To date, information on bone quality (three-dimensional microarchitecture) and, thus, bone strength is scarce. We observed decreased...
UNLABELLED
Liver cirrhosis leads to bone loss. To date, information on bone quality (three-dimensional microarchitecture) and, thus, bone strength is scarce. We observed decreased bone quality at both assessed sites, independent of disease severity. Therefore, all patients should undergo early-stage screening for osteoporosis.
INTRODUCTION
Recent studies found low bone mineral density in cirrhosis, but data on bone microstructure are scarce. This study assessed weight-bearing and non-weight-bearing bones in patients with cirrhosis and healthy controls. The primary objective was to evaluate trabecular and cortical microarchitecture.
METHODS
This was a single-center study in patients with recently diagnosed hepatic cirrhosis. Thirty-two patients and 32 controls participated in this study. After determining the type of cirrhosis, the parameters of bone microarchitecture were assessed by high-resolution peripheral quantitative computed tomography.
RESULTS
Both cortical and trabecular microarchitectures showed significant alterations. At the radius, trabecular bone volume fraction was 17% lower (corrected p = 0.028), and, at the tibia, differences were slightly more pronounced. Trabecular bone volume fraction was 19% lower (p = 0.024), cortical bone mineral density 7% (p = 0.007), and cortical thickness 28% (p = 0.001), while cortical porosity was 32% higher (p = 0.023), compared to controls. Areal bone mineral density was lower (lumbar spine - 13%, total hip - 11%, total body - 9%, radius - 17%, and calcaneus - 26%). There was no correlation between disease severity and microarchitecture. Areal bone mineral density (aBMD) measured by dual-energy X-ray absorptiometry (DXA) correlated well with parameters of cortical and trabecular microarchitecture.
CONCLUSIONS
Hepatic cirrhosis deteriorates both trabecular and cortical microarchitecture, regardless of disease severity. Areal bone mineral density is diminished at all sites as a sign of generalized affection. In patients with hepatic cirrhosis, regardless of its origin or disease severity, aBMD measurements are an appropriate tool for osteologic screening.
Topics: Aged; Biomarkers; Bone Density; Bone Remodeling; Cancellous Bone; Case-Control Studies; Cortical Bone; Female; Humans; Liver Cirrhosis; Liver Cirrhosis, Alcoholic; Male; Middle Aged; Porosity; Radius; Tibia; Tomography, X-Ray Computed; Weight-Bearing
PubMed: 30788527
DOI: 10.1007/s00198-019-04870-6 -
Advances in Experimental Medicine and... 2022Recent advances in imaging of bone microstructure have led to a growing recognition of the role of cortical microstructure in osteoporosis. It is now accepted that the...
Recent advances in imaging of bone microstructure have led to a growing recognition of the role of cortical microstructure in osteoporosis. It is now accepted that the assessment of the microstructure of cortical porosity is essential to assess bone mechanical competence and predict fracture risk. Cortical porosity affects the propagation of ultrasound waves because pores act as ultrasound scatterers. Scattering by the porosity is an opportunity that should be leveraged to extract quantitative information about cortical microstructure. Scattering by the pores affects a number of ultrasound parameters that should be quantified, including attenuation, backscatter coefficient, ultrasound diffusivity, and their frequency dependence. Measuring these ultrasound parameters and developing models that describe their dependence upon parameters of cortical microstructure is the key to solve inverse problems that will allow the quantitative assessment of cortical porosity and ultimately will improve the non-invasive ultrasound-based evaluation of bone mechanical competence and fracture risk. In this chapter, we present recent advances in measuring and modeling those parameters in cortical bone.
Topics: Bone Density; Bone and Bones; Cortical Bone; Fractures, Bone; Humans; Osteoporosis; Porosity; Ultrasonography
PubMed: 35508876
DOI: 10.1007/978-3-030-91979-5_9 -
Current Osteoporosis Reports Feb 2020This review updates readers on recent developments in the assessment of cortical bone fragility in vivo. The review explains the clinical need that motivated the... (Review)
Review
PURPOSE OF REVIEW
This review updates readers on recent developments in the assessment of cortical bone fragility in vivo. The review explains the clinical need that motivated the development of Cortical Bone Mechanics Technology™ (CBMT) as a scientific instrument, its unique capabilities, and its necessary further development as a medical device.
RECENT FINDINGS
Clinical experience with dual-energy X-ray absorptiometry has led to calls for new clinical methods for assessing bone health. CBMT is a noninvasive, dynamic 3-point bending test that makes direct, functional measurements of the mechanical properties of cortical bone in ulnas of living people. Its technical validity in accurate measurements of ulna flexural rigidity and its clinical validity in accurate estimations of quasistatic ulna bending strength have been demonstrated. Because CBMT is a whole bone test, its measurements reflect the influences of bone quantity and bone quality at all hierarchical levels.
Topics: Absorptiometry, Photon; Biomechanical Phenomena; Cortical Bone; Flexural Strength; Humans; Ulna; Weight-Bearing
PubMed: 32088857
DOI: 10.1007/s11914-020-00558-7