woven bone [keywords]
- Elastic properties of woven bone: effect of mineral content and collagen fibrils orientation. [JOURNAL ARTICLE]
- Biomech Model Mechanobiol 2016 Jul 8.
Woven bone is a type of tissue that forms mainly during fracture healing or fetal bone development. Its microstructure can be modeled as a composite with a matrix of mineral (hydroxyapatite) and inclusions of collagen fibrils with a more or less random orientation. In the present study, its elastic properties were estimated as a function of composition (degree of mineralization) and fibril orientation. A self-consistent homogenization scheme considering randomness of inclusions' orientation was used for this purpose. Lacuno-canalicular porosity in the form of periodically distributed void inclusions was also considered. Assuming collagen fibrils to be uniformly oriented in all directions led to an isotropic tissue with a Young's modulus [Formula: see text] GPa, which is of the same order of magnitude as that of woven bone in fracture calluses. By contrast, assuming fibrils to have a preferential orientation resulted in a Young's modulus in the preferential direction of 9-16 GPa depending on the mineral content of the tissue. These results are consistent with experimental evidence for woven bone in foetuses, where collagen fibrils are aligned to a certain extent.
- A Single Chance to Contact Multiple Targets: Distinct Osteocyte Morphotypes Shed Light on the Cellular Mechanism Ensuring the Robust Formation of Osteocytic Networks. [JOURNAL ARTICLE]
- J Exp Zool B Mol Dev Evol 2016 Jul 6.
The formation of the complex osteocytic network relies on the emission of long cellular processes involved in communication, mechanical strain sensing, and bone turnover control. Newly deposited osteocytic processes rapidly become trapped within the calcifying matrix, and, therefore, they must adopt their definitive conformation and contact their targets in a single morphogenetic event. However, the cellular mechanisms ensuring the robustness of this unique mode of morphogenesis remain unknown. To address this issue, we examined the developing calvaria of the amphibian Xenopus tropicalis by confocal, two-photon, and super-resolution imaging, and described flattened osteocytes lying within a woven bone structured in lamellae of randomly oriented collagen fibers. While most cells emit peripheral and perpendicular processes, we report two osteocytes morphotypes, located at different depth within the bone matrix and exhibiting distinct number and orientation of perpendicular cell processes. We show that this pattern is conserved with the chick Gallus gallus and suggest that the cellular microenvironment, and more particularly cell-cell contact, plays a fundamental role in the induction and stabilization of osteocytic processes. We propose that this intrinsic property might have been evolutionarily selected for its ability to robustly generate self-organizing osteocytic networks harbored by the wide variety of bone shapes and architectures found in extant and extinct vertebrates.
- Mandibular Cartilage Collagen Network Nanostructure: Insights for Regeneration. [Journal Article]
- Cartilage 2016 Jul; 7(3):274-83.
Mandibular condyle cartilage (MCC) has a unique structure among articular cartilages; however, little is known about its nanoscale collagen network architecture, hampering design of regeneration therapies and rigorous evaluation of regeneration experiment outcomes in preclinical research. Helium ion microscopy is a novel technology with a long depth of field that is uniquely suited to imaging open 3D collagen networks at multiple scales without obscuring conductive coatings.The objective of this research was to image, at the micro- and nanoscales, the depth-dependent MCC collagen network architecture.MCC was collected from New Zealand white rabbits. Images of MCC zones were acquired using helium ion, transmission electron, and light microscopy. Network fibril and canal diameters were measured.For the first time, the MCC was visualized as a 3D collagen fibril structure at the nanoscale, the length scale of network assembly. Fibril diameters ranged from 7 to 110 nm and varied by zone. The articular surface was composed of a fine mesh that was woven through thin layers of larger fibrils. The fibrous zone was composed of approximately orthogonal lamellae of aligned fibrils. Fibrocyte processes surrounded collagen bundles forming extracellular compartments. The proliferative, mature, and hypertrophic zones were composed of a branched network that was progressively remodeled to accommodate chondrocyte hypertrophy. Osteoid fibrils were woven around osteoblast cytoplasmic processes to create numerous canals similar in size to canaliculi of mature bone.This multiscale investigation advances our foundational understanding of the complex, layered 3D architecture of the MCC collagen network.
- Osteonecrosis of the jaws (ONJ) in mice after extraction of teeth with periradicular disease. [JOURNAL ARTICLE]
- Bone 2016 Jun 18.:133-141.
Osteonecrosis of the jaws (ONJ) is a complication of antiresorptive medications, such as denosumab or bisphosphonates, prescribed to patients with bone malignancy or osteoporosis. The most common instigating local factor in ONJ pathogenesis is tooth extraction. However, in adults the great majority of teeth are extracted due to dental disease. Here, we have investigated alveolar bone healing after extraction of healthy teeth or teeth with naturally occurring periradicular disease in mice treated with high dose zoledronic acid (ZA), a potent bisphosphonate, or OPG-Fc, a RANKL inhibitor. C57BL/6 mice were treated for eight weeks and in vivo micro-CT was performed to identify spontaneously occurring periradicular lesions around the roots of maxillary molars. Then, extractions of molars with and without dental disease were performed in all groups. Four weeks later, animals were euthanized and maxillae were dissected and analyzed. Clinically, all vehicle animals with extraction of healthy or diseased teeth, and most OPG-Fc or ZA animals with extraction of healthy teeth showed normal mucosal healing. On the contrary, most animals with OPG-Fc or ZA treatment and extraction of diseased teeth demonstrated impaired healing with visible mucosal defects. Radiographically, bone socket healing was significantly compromised in OPG-Fc and ZA-treated mice with periradicular disease in comparison to other groups. Histologically, all vehicle animals showed normal mucosal healing and socket remodeling. OPG-Fc and ZA animals with extraction of healthy teeth showed normal mucosal healing, woven bone formation in the socket, and decreased remodeling of the original socket confines. OPG-Fc and ZA animals with extraction of diseased teeth showed mucosal defects, persistent prominent inflammatory infiltrate, bone exposure and areas of osteonecrosis. These findings support that dental disease is critical in the pathogenesis of ONJ, not only as the instigating cause for tooth extraction, but also as a compounding factor in ONJ development and pathophysiology.
- Pediatric Chronic Nonbacterial Osteomyelitis of the Jaw: Clinical, Radiographic, and Histopathologic Features. [JOURNAL ARTICLE]
- J Oral Maxillofac Surg 2016 May 26.
Chronic nonbacterial osteomyelitis (CNO) is a focal sterile inflammatory osteitis in children that most commonly develops in the long bones, but can occur in any bone. The disease course is variable, ranging from acute and self-resolving isolated lesions to chronic recurrent multifocal osteomyelitis (CRMO), which is frequently associated with extraosseous inflammatory disease. The purpose of this study was to present our clinical experience with CNO of the mandible in children. The specific aims were to 1) document the clinical characteristics, radiographic findings, and histologic features of CNO and 2) determine the percentage of our sample with multifocal disease (CRMO).This is a retrospective case series of patients with mandibular CNO. To be included, patients had to have a mandibular lesion radiographically consistent with osteomyelitis without infection, onset before aged 18 years, and complete records. Medical records were reviewed for history, clinical features, imaging, and pathology. Descriptive data were summarized.The sample included 22 patients (13 female and 9 male patients) with disease onset at a mean age of 9.05 ± 2.4 years. On presentation, all patients reported mandibular pain and swelling, and 45% had trismus. All had clinical and/or radiographic findings of multifocal intraosseous disease and/or extraosseous inflammatory lesions. Of the patients, 12 (54%) had a documented family history of autoimmune or autoinflammatory disease and 15 (68%) had elevated erythrocyte sedimentation rates during a flare. Computed tomography scans typically showed expansion of the affected mandible with sclerosis of the medullary space, small foci of poorly defined lytic destruction with a lamellated periosteal reaction, and swollen muscles of mastication. Four distinct histologic features were noted including parallel and interconnected osteoid seams, atypical osteoid, areas of woven bone and hypocellular fibroblastic stroma resembling fibrous dysplasia, and patchy nodular fibrosis.Pediatric CNO of the mandible has characteristic radiographic and pathologic features and is usually found as one of multiple disease foci in CRMO rather than as an isolated lesion.
- Fibrous Dysplasia with Massive Cartilaginous Differentiation (Fibrocartilaginous Dysplasia) in the Proximal Femur: A Case Report and Review of the Literature. [Journal Article]
- Case Rep Oncol 2016 Jan-Apr; 9(1):126-33.
Fibrous dysplasia (FD) is a monostotic or polyostotic benign bone lesion with spindle-cell proliferation in woven bone and stroma. Rarely, cartilaginous differentiation can be seen in the lesions of FD. FD with massive cartilaginous differentiation is called fibrocartilaginous dysplasia (FCD) and is considered a rare variant of FD. Although pathological findings of FD show irregular immature bone formation without osteoblastic rimming in fibrous tissue, and rarely show very small amounts of cartilage, histological images of FCD are said to show that cartilage with a relatively high cell density is present in the majority and that FD-like findings are seen in parts of it. The most characteristic feature of FCD on images is calcification in the lesions reflecting cartilaginous tissue. On the other hand, typical radiographic findings of FD include shadows with a ground-glass appearance and thinning and bulging of the cortical bone, the observation if calcification is not usual. Therefore, in the diagnosis of FCD, differentiation from multiple enchondromatosis, Ollier disease, chondrosarcoma, and chondrosarcoma secondary to FD is necessary, and it seems important to make a careful diagnosis based not only on the pathological findings but also on imaging and clinical findings. Herein, we report on a case of FD of the proximal femur associated with intralesional extensive carti laginous differentiation in which a pathological fracture occurred during follow-up, with a review of the literature.
- A biomimetic multilayer nanofiber fabric fabricated by electrospinning and textile technology from polylactic acid and Tussah silk fibroin as a scaffold for bone tissue engineering. [Journal Article]
- Mater Sci Eng C Mater Biol Appl 2016 Oct 1.:599-610.
To engineer bone tissue, a scaffold with good biological properties should be provided to approximate the hierarchical structure of collagen fibrils in natural bone. In this study, we fabricated a novel scaffold consisting of multilayer nanofiber fabrics (MLNFFs) by weaving nanofiber yarns of polylactic acid (PLA) and Tussah silk fibroin (TSF). The yarns were fabricated by electrospinning, and we found that spinnability, as well as the mechanical properties of the resulting scaffold, was determined by the ratio between polylactic acid and Tussah silk fibroin. In particular, a 9:1 mixture can be spun continuously into nanofiber yarns with narrow diameter distribution and good mechanical properties. Accordingly, woven scaffolds based on this mixture had excellent mechanical properties, with Young's modulus 417.65MPa and tensile strength 180.36MPa. For nonwoven scaffolds fabricated from the same materials, the Young's modulus and tensile strength were 2- and 4-fold lower, respectively. Woven scaffolds also supported adhesion and proliferation of mouse mesenchymal stem cells, and promoted biomineralization via alkaline phosphatase and mineral deposition. Finally, the scaffolds significantly enhanced the formation of new bone in damaged femoral condyle in rabbits. Thus, the scaffolds are potentially suitable for bone tissue engineering because of biomimetic architecture, excellent mechanical properties, and good biocompatibility.
- Severe muscle trauma triggers heightened and prolonged local musculoskeletal inflammation and impairs adjacent tibia fracture healing. [Journal Article]
- J Musculoskelet Neuronal Interact 2016; 16(2):122-34.
Complicated fracture healing is often associated with the severity of surrounding muscle tissue trauma. Since inflammation is a primary determinant of musculoskeletal health and regeneration, it is plausible that delayed healing and non-unions are partly caused by compounding local inflammation in response to concomitant muscle trauma.To investigate this possibility, a Lewis rat open fracture model [tibia osteotomy with adjacent tibialis anterior (TA) muscle volumetric muscle loss (VML) injury] was interrogated. We observed that VML injury impaired tibia healing, as indicated by diminished mechanical strength and decreased mineralized bone within the fracture callus, as well as continued presence of cartilage instead of woven bone 28 days post-injury. The VML injured muscle presented innate and adaptive immune responses that were atypical of canonical muscle injury healing. Additionally, the VML injury resulted in a perturbation of the inflammatory phase of fracture healing, as indicated by elevations of CD3(+) lymphocytes and CD68+ macrophages in the fracture callus at 3 and 14d post-injury, respectively.These data indicate that heightened and sustained innate and adaptive immune responses to traumatized muscle are associated with impaired fracture healing and may be targeted for the prevention of delayed and non-union following musculoskeletal trauma.
- Bone marrow lesions in hip osteoarthritis are characterized by increased bone turnover and enhanced angiogenesis. [JOURNAL ARTICLE]
- Osteoarthritis Cartilage 2016 May 24.
Bone marrow lesions (BML), previously denoted bone marrow edema, are detected as water signals by magnetic resonance imaging (MRI). Previous histologic studies were unable to demonstrate any edematous changes at the tissue level. Therefore, our aim was to investigate the underlying biological mechanisms of the water signal in MRI scans of bone affected by BML.Tetracycline labeling in addition to water sensitive MRI scans of 30 patients planned for total hip replacement surgery was undertaken. Twenty-one femoral heads revealed BML on MRI, while nine were negative and used as controls (CON). Guided by the MRI images cylindrical biopsies were extracted from areas with BML in the femoral heads. Tissue sections from the biopsies were subjected to histomorphometric image analyses of the cancellous bone envelope.Patients with BML exhibited an average 40- and 18-fold increase of bone formation rate and mineralizing surface, respectively. Additionally, samples with BML demonstrated 2-fold reduction of marrow fat and 28-fold increase of woven bone. Immunohistochemical analysis showed a 4-fold increase of angiogenesis markers CD31 and von Willebrand Factor (vWF) in the BML-group compared to CON.This study indicates that BML are characterized by increased bone turnover, vascularity and angiogenesis in keeping with it being a reparatory process. Thus, the water signal, which is the hallmark of BML on MRI, is most probably reflecting increased tissue vascularity accompanying increased remodeling activity.
- CD169(+) macrophages mediate pathological formation of woven bone in skeletal lesions of prostate cancer. [Journal Article]
- J Pathol 2016 Jun; 239(2):218-30.
Skeletal metastases present a major clinical challenge for prostate cancer patient care, inflicting distinctive mixed osteoblastic and osteolytic lesions that cause morbidity and refractory skeletal complications. Macrophages are abundant in bone and bone marrow and can influence both osteoblast and osteoclast function in physiology and pathology. Herein, we examined the role of macrophages in prostate cancer bone lesions, particularly the osteoblastic response. First, macrophage and lymphocyte distributions were qualitatively assessed in patient's prostate cancer skeletal lesions by immunohistochemistry. Second, macrophage functional contributions to prostate tumour growth in bone were explored using an immune-competent mouse model combined with two independent approaches to achieve in vivo macrophage depletion: liposome encapsulated clodronate that depletes phagocytic cells (including macrophages and osteoclasts); and targeted depletion of CD169(+) macrophages using a suicide gene knock-in model. Immunohistochemistry and histomorphometric analysis were performed to quantitatively assess cancer-induced bone changes. In human bone metastasis specimens, CD68(+) macrophages were consistently located within the tumour mass. Osteal macrophages (osteomacs) were associated with pathological woven bone within the metastatic lesions. In contrast, lymphocytes were inconsistently present in prostate cancer skeletal lesions and when detected, had varied distributions. In the immune-competent mouse model, CD169(+) macrophage ablation significantly inhibited prostate cancer-induced woven bone formation, suggesting that CD169(+) macrophages within pathological woven bone are integral to tumour-induced bone formation. In contrast, pan-phagocytic cell, but not targeted CD169(+) macrophage depletion resulted in increased tumour mass, indicating that CD169(-) macrophage subset(s) and/or osteoclasts influenced tumour growth. In summary, these observations indicate a prominent role for macrophages in prostate cancer bone metastasis that may be therapeutically targetable to reduce the negative skeletal impacts of this malignancy, including tumour-induced bone modelling. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.