-
Matrix Biology : Journal of the... 2016There is an ongoing need for effective materials that can replace autologous bone grafts in the clinical treatment of bone injuries and deficiencies. In recent years,... (Review)
Review
There is an ongoing need for effective materials that can replace autologous bone grafts in the clinical treatment of bone injuries and deficiencies. In recent years, research efforts have shifted away from a focus on inert biomaterials to favor scaffolds that mimic the biochemistry and structure of the native bone extracellular matrix (ECM). The expectation is that such scaffolds will integrate with host tissue and actively promote osseous healing. To further enhance the osteoinductivity of bone graft substitutes, ECM-mimetic scaffolds are being engineered with a range of growth factors (GFs). The technologies used to generate GF-modified scaffolds are often inspired by natural processes that regulate the association between endogenous ECMs and GFs. The purpose of this review is to summarize research centered on the development of regenerative scaffolds that replicate the fundamental collagen-hydroxyapatite structure of native bone ECM, and the functionalization of these scaffolds with GFs that stimulate critical events in osteogenesis.
Topics: Biological Mimicry; Bone Matrix; Bone Substitutes; Cell Differentiation; Cell Proliferation; Humans; Intercellular Signaling Peptides and Proteins; Osteogenesis; Regenerative Medicine; Tissue Engineering; Tissue Scaffolds
PubMed: 26940231
DOI: 10.1016/j.matbio.2016.02.011 -
Calcified Tissue International Aug 2017Matrix maturation within cortical bone is an important but oft-neglected component of bone remodeling because of the lack of a suitable small animal model....
Matrix maturation within cortical bone is an important but oft-neglected component of bone remodeling because of the lack of a suitable small animal model. Intra-cortical remodeling can be induced in rodents by feeding virgin or lactating animals a low-calcium diet. The current study aimed to determine which of these two models is most suitable for studying intra-cortical matrix maturation. We compared intra-cortical remodeling in female rats fed a normal calcium diet (virgin/normal Ca), a low-calcium diet (virgin/low Ca), or a low-calcium diet during lactation (lactation/low Ca). The low-calcium diet was administered for 23 days (induction phase) followed by return to normal calcium for 30 days (recovery phase). At the end of induction, the virgin/normal Ca and virgin/low-Ca animals had no difference in cortical porosity, but the lactation/low-Ca animals had elevated cortical porosity at various diaphyseal sites in the femur and tibia. The distal femoral site had the greatest amount of induced porosity in the size range of rat secondary osteons. Neither global mineralization nor tissue age-specific mineral-to-matrix ratio in the bone formed during recovery were affected in the lactation/low-Ca rats. Serum calcium levels did not differ from controls, but phosphate levels were slightly elevated, consistent with the rapid recovery of lost bone mass. We conclude that the lactation/low-Ca model represents a means to increase intra-cortical remodeling in adult rats with no apparent detrimental effect on matrix maturation. This model will provide researchers with a new tool to study matrix maturation throughout the cortex.
Topics: Animals; Bone Density; Bone Matrix; Bone Remodeling; Bone and Bones; Calcium; Calcium, Dietary; Female; Lactation; Rats
PubMed: 28374176
DOI: 10.1007/s00223-017-0270-7 -
Journal of Bone and Mineral Research :... Mar 2017Osteoblasts secrete matrix vesicles and proteins to bone surfaces, but the molecular mechanisms of this secretion system remain unclear. The present findings reveal the...
Osteoblasts secrete matrix vesicles and proteins to bone surfaces, but the molecular mechanisms of this secretion system remain unclear. The present findings reveal the roles of important genes in osteoblasts involved in regulation of extracellular matrix secretion. We especially focused on "soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein receptor" (SNARE) genes and identified notable Syntaxin 4a (Stx4a) expression on the basolateral side of the plasma membrane of osteoblasts. Furthermore, Stx4a overexpression was found to increase mineralization by osteoblastic cells, whereas Stx4a knockdown reduced levels of mineralization. Also, BMP-4 and IGF-1 induced the localization of Stx4a to the basolateral side of the cells. To examine the function of Stx4a in osteoblasts, we generated osteoblast-specific Stx4a conditional knockout mice, which demonstrated an osteopenic phenotype due to reduced matrix secretion. Bone mineral density, shown by peripheral quantitative computed tomography (pQCT), was reduced in the femur metaphyseal and diaphyseal regions of Stx4a osteoblast-specific deficient mice, whereas bone parameters, shown by micro-computed tomography (μCT) and bone histomorphometric analysis, were also decreased in trabecular bone. In addition, primary calvarial cells from those mice showed decreased mineralization and lower secretion of matrix vesicles. Our findings indicate that Stx4a plays a critical role in bone matrix production by osteoblasts. © 2016 American Society for Bone and Mineral Research.
Topics: Animals; Animals, Newborn; Bone Density; Bone Matrix; Calcification, Physiologic; Cytoplasmic Vesicles; Mice, Knockout; Osteoblasts; Qa-SNARE Proteins; Skull; Tibia; X-Ray Microtomography
PubMed: 27933643
DOI: 10.1002/jbmr.3056 -
Bone Sep 2022Overweightness and obesity in adolescents are epidemics linked to chronic low-grade inflammation and elevated fracture risk. The increased fracture risk observed in...
Overweightness and obesity in adolescents are epidemics linked to chronic low-grade inflammation and elevated fracture risk. The increased fracture risk observed in overweight/obese adolescence contrasts the traditional concept that high body mass is protective against fracture, and thus highlights the need to determine why weight gain becomes detrimental to fracture during growth and maturity. The Receptor for Advanced Glycation End products (RAGE) is a central inflammatory regulator that can influence bone metabolism. It remains unknown how RAGE removal impacts skeletal fragility in overweightness/obesity, and whether increased fracture risk in adolescents could result from low-grade inflammation deteriorating bone quality. We characterized the multiscale structural, mechanical, and chemical properties of tibiae extracted from adolescent C57BL/6J (WT) and RAGE null (KO) mice fed either low-fat (LF) or high-fat (HF) diet for 12 weeks starting at 6 weeks of age using micro-computed tomography, strength, Raman spectroscopy, and nanoindentation. Overweight/obese WT HF mice possessed degraded mineral-crystal quality and increased matrix glycoxidation in the form of pentosidine and carboxymethyl-lysine, with HF diet in females only showing reduced cortical surface expansion and TMD independently of RAGE ablation. Furthermore, in contrast to males, HF diet in females led to more material damage and plastic deformation. RAGE KO mitigated glycoxidative matrix accumulation, preserved mineral quantity, and led to increased E/H ratio in females. Taken together, these results highlight the complex, multi-scale and sex-dependent relationships between bone quality and function under overweightness, and identifies RAGE-controlled glycoxidation as a target to potentially preserve matrix quality and mechanical integrity.
Topics: Animals; Bone Matrix; Diet, High-Fat; Disease Models, Animal; Female; Glycation End Products, Advanced; Inflammation; Male; Mice; Mice, Inbred C57BL; Obesity; Overweight; Receptor for Advanced Glycation End Products; X-Ray Microtomography
PubMed: 35718325
DOI: 10.1016/j.bone.2022.116470 -
Advanced Biology Jan 2021Demineralized bone matrix (DBM), a potential alternative to autologous bone-graft, has been increasingly used for clinical bone repair; however, its application in...
Demineralized bone matrix (DBM), a potential alternative to autologous bone-graft, has been increasingly used for clinical bone repair; however, its application in larger defects isn't successful partly due to the rapid dispersion of DBM particles and relatively lower osteoinductivity. Here, a novel strategy is created to complement the osteoinductivity of DBM by incorporating DBM in biopolymer hydrogel combined with the abrogation of BMP antagonism. Combined treatment of DBM + noggin-suppression displays increased osteogenic potency of human bone marrow mesenchymal stem cells (hBMSCs) . Injectable chitosan (MeGC)-based hydrogel with heparinization (Hep-MeGC) is further developed to localize and stabilize DBM. Noggin-suppression reveals the significant increase in osteogenesis of hBMSCs in the photopolymerizable Hep-MeGC hydrogels with the encapsulation of DBM. Moreover, the combination of DBM + noggin-suppression in the injectable Hep-MeGC hydrogel displays a robust bone healing in mouse critical-sized calvarial defects . The mechanistic analysis demonstrates that noggin-suppression increased DBM osteoinductivity by stimulating endogenous BMP/Smad signals. These results have shown promise in DBM's ability as a prominent bone grafting material while being coupled with gene editing mechanism and a localizing three-dimensional scaffold. Together, this approach poses a significant increase in the efficiency of DBM-mediated craniofacial bone repair and dental osteointegration.
Topics: Animals; Bone Matrix; Hydrogels; Mesenchymal Stem Cells; Mice; Osteogenesis; Polymers
PubMed: 33585837
DOI: 10.1002/adbi.202000135 -
Journal of Biomedical Materials... Apr 2020Autogenous bone grafting requires a donor site and may lose substantial volume during remodeling. Several bone replacement materials (BRMs) are under development to...
Autogenous bone grafting requires a donor site and may lose substantial volume during remodeling. Several bone replacement materials (BRMs) are under development to overcome these limitations, especially for indications for minimally intervention surgeries. The objective of our study was to assess the potential of an equine collagen cone reinforced with biphasic calcium phosphate (CC-BCP) particles and deproteinized bovine bone matrix (BBM) coated with polylactic acid, and poly-ε-caprolactone copolymer (BBM-PCC) and then to compare the outcomes with a deproteinized BBM and an equine CC without a filler in a sheep sinus grafting model in the Elleven female sheep were selected. Two experimental sites on each side of the animals were prepared using an extraoral approach for maxillary sinus wall. The four treatments were performed in each animal through a standardized 10-mm access window. While the BBM access was covered with a collagen membrane, all other sites were closed with an equine collagen membrane. All animals were euthanized after 16 weeks. New bone (NB), residual graft particles, and connective tissue were measured in undemineralized resin-embedded sections. As a result, one sheep did not survive the surgery. All sites in the remaining 10 sheep healed uneventfully. All CC and BBM-PCC grafts resorbed and failed to augment the sinuses. BBM and CC-BCP, in contrast, showed some histologic evidence of NB and surgical site augmentation. The NB fraction in the latter two groups accounted for 10 ± 9 and 4 ± 5%, respectively (p > 0.05). In conclusion, BBM-PCC and collagen cone performed poorly for sinus floor augmentation, while deproteinised BBM and reinforced collagen cone demonstrated comparable outcomes.
Topics: Animals; Bone Matrix; Bone Substitutes; Bone Transplantation; Cattle; Coated Materials, Biocompatible; Collagen; Female; Humans; Hydroxyapatites; Maxillary Sinus; Membranes, Artificial; Models, Animal; Polyesters; Sheep; Sinus Floor Augmentation
PubMed: 31199055
DOI: 10.1002/jbm.b.34429 -
Regenerative Medicine Apr 2020The objectives of this study were to develop a new decellularized bone matrix (DBM) and to investigate its effect on the cell behavior of human bone marrow-derived...
The objectives of this study were to develop a new decellularized bone matrix (DBM) and to investigate its effect on the cell behavior of human bone marrow-derived mesenchymal stem cells (hMSCs), compared with porous β-tricalcium phosphate (β-TCP) scaffolds. Triton X-100 and deoxycholate sodium solution, combining DNase I and RNase, were used to decellularize porcine bones. The DBM were then characterized by DNA contents and matrix components. hMSCs were then seeded on the DBM and β-TCP scaffolds to study cell behavior. Results showed that most porcine cells were removed and the matrix components of the DBM were maintained. Cell culture results showed that DBM promoted cell attachment and proliferation of hMSCs but did not significantly promote the gene expression of osteogenic genes, compared with β-TCP scaffolds. DBM has similar function on cell behavior to β-TCP scaffolds that have promising potential in bone tissue regeneration.
Topics: Animals; Bone Matrix; Bone Regeneration; Cell Differentiation; Cell Proliferation; Cells, Cultured; Extracellular Matrix; Humans; Mesenchymal Stem Cells; Swine; Tissue Engineering; Tissue Scaffolds
PubMed: 32441554
DOI: 10.2217/rme-2019-0125 -
Current Osteoporosis Reports Jun 2016Magnetic resonance imaging (MRI) plays a pivotal role for assessment of the musculoskeletal system. It is currently the clinical modality of choice for evaluation of... (Review)
Review
Magnetic resonance imaging (MRI) plays a pivotal role for assessment of the musculoskeletal system. It is currently the clinical modality of choice for evaluation of soft tissues including cartilage, ligaments, tendons, muscle, and bone marrow. By comparison, the study of calcified tissue by MRI is still in its infancy. In this article, we review the potential of the modality for assessment of cortical bone properties known to be affected in degenerative bone disease, with focus on parameters related to matrix and mineral densities, and porosity, by means of emerging solid-state (1)H and (31)P MRI techniques. In contrast to soft tissues, the MRI signal in calcified tissues has very short lifetime, on the order of 100 μs to a few milliseconds, demanding customized imaging approaches that allow capture of the signal almost immediately after excitation. The technologies described are suited for quantitatively imaging human cortical bone in specimens as well as in vivo in patients on standard clinical imagers, yielding either concentrations in absolute units when measured against a reference standard, or more simply, in the form of surrogate biomarkers. The two major water fractions in cortical bone are those of collagen-bound and pore water occurring at an approximately 3:1 ratio. Collagen-bound water density provides a direct quantitative measure of osteoid density. While at an earlier stage of development, quantification of mineral phosphorus by (31)P MRI yields mineral density and, together with knowledge of matrix density, should allow quantification of the degree of bone mineralization.
Topics: Bone Density; Bone Matrix; Bone and Bones; Calcification, Physiologic; Collagen; Cortical Bone; Extracellular Matrix; Humans; Hydrogen; Magnetic Resonance Imaging; Phosphorus Isotopes; Porosity; Water
PubMed: 27048472
DOI: 10.1007/s11914-016-0307-2 -
Scientific Reports Apr 2017Vascularization is crucial for bone regeneration after the transplantation of tissue-engineered bone grafts in the clinical setting. Growing evidence suggests that...
Vascularization is crucial for bone regeneration after the transplantation of tissue-engineered bone grafts in the clinical setting. Growing evidence suggests that mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) are potently pro-angiogenic both in vitro and in vivo. In the current study, we fabricated a novel EV-functionalized scaffold with enhanced pro-angiogenic and pro-bone regeneration activities by coating decalcified bone matrix (DBM) with MSC-derived EVs. EVs were harvested from rat bone marrow-derived MSCs and the pro-angiogenic potential of EVs was investigated in vitro. DBM scaffolds were then coated with EVs, and the modification was verified by scanning electron microscopy and confocal microscopy. Next, the pro-angiogenic and pro-bone regeneration activities of EV-modified scaffolds were evaluated in a subcutaneous bone formation model in nude mice. Micro-computed tomography scanning analysis showed that EV-modified scaffolds with seeded cells enhanced bone formation. Enhanced bone formation was confirmed by histological analysis. Immunohistochemical staining for CD31 proved that EV-modified scaffolds promoted vascularization in the grafts, thereby enhancing bone regeneration. This novel scaffold modification method provides a promising way to promote vascularization, which is essential for bone tissue engineering.
Topics: Animals; Bone Matrix; Bone Regeneration; Calcification, Physiologic; Cells, Cultured; Extracellular Vesicles; Humans; Male; Mesenchymal Stem Cells; Mice, Nude; Neovascularization, Physiologic; Osteogenesis; Rats; Rats, Sprague-Dawley; Tissue Engineering; Tissue Scaffolds; X-Ray Microtomography
PubMed: 28367979
DOI: 10.1038/srep45622 -
Frontiers in Immunology 2023Cathepsins are a type of lysosomal globulin hydrolase and are crucial for many physiological processes, including the resorption of bone matrix, innate immunity,... (Review)
Review
Cathepsins are a type of lysosomal globulin hydrolase and are crucial for many physiological processes, including the resorption of bone matrix, innate immunity, apoptosis, proliferation, metastasis, autophagy, and angiogenesis. Findings regarding their functions in human physiological processes and disorders have drawn extensive attention. In this review, we will focus on the relationship between cathepsins and oral diseases. We highlight the structural and functional properties of cathepsins related to oral diseases, as well as the regulatory mechanisms in tissue and cells and their therapeutic uses. Elucidating the associated mechanism between cathepsins and oral diseases is thought to be a promising strategy for the treatment of oral diseases and may be a starting point for further studies at the molecular level.
Topics: Humans; Cathepsins; Mouth Diseases; Apoptosis; Immunity, Innate; Bone Matrix
PubMed: 37334378
DOI: 10.3389/fimmu.2023.1203071