-
International Journal of Oral Science Jun 2009With additional functions of osteocytes being identified, the concept that osteocytes are just "static lacunar-dwelling cells" is no longer accepted. We reviewed most of... (Review)
Review
With additional functions of osteocytes being identified, the concept that osteocytes are just "static lacunar-dwelling cells" is no longer accepted. We reviewed most of the relevant literature on osteocyte's function in the direct remodeling of the perilucunar matrix, discussing the advantages and disadvantages. Special attention was paid to how the negative researchers argue about the "osteocytic osteolysis" principle, and how the positive side addressed the arguments. We also discussed the newly found data of osteocytic remodeling function from our group. With more biotechnology in hand, there is increased excitement in the prospect of now being able to answer the two important questions: do osteocytes have the capability to remove mineral from the perilacunar matrix and if so what are the molecular and cellular mechanisms? do osteocytes have the capability to deposit new mineral on the perilacunar matrix and if so what are the cellular and molecular mechanisms?
Topics: Animals; Bone Matrix; Bone Remodeling; Humans; Osteocytes; Osteogenesis; Osteolysis
PubMed: 20687297
DOI: 10.4248/ijos.09019 -
Calcified Tissue International Dec 2022Osteoid is a layer of new-formed bone that is deposited on the bone border during the process of new bone formation. This deposition process is crucial for bone tissue,...
Osteoid is a layer of new-formed bone that is deposited on the bone border during the process of new bone formation. This deposition process is crucial for bone tissue, and flaws in it can lead to bone diseases. Certain bone diseases, i.e. medication related osteonecrosis, are overexpressed in mandibular bone. Because mandibular bone presents different properties than other bone types, the data concerning osteoid formation in other bones are inapplicable for human-mandibular bone. Previously, the molecular distribution of other bone types has been presented using Fourier-transform infrared (FTIR) spectroscopy. However, the spatial distribution of molecular components of healthy-human-mandibular-bone osteoid in relation to histologic landmarks has not been previously presented and needs to be studied in order to understand diseases that occur human-mandibular bone. This study presents for the first time the variation in molecular distribution inside healthy-human-mandibular-bone osteoid by juxtaposing FTIR data with its corresponding histologic image obtained by autofluorescence imaging of its same bone section. During new bone formation, bone-forming cells produce an osteoid constituted primarily of type I collagen. It was observed that in mandibular bone, the collagen type I increases from the osteoblast line with the distance from the osteoblasts, indicating progressive accumulation of collagen during osteoid formation. Only later inside the collagen matrix, the osteoid starts to mineralize. When the mineralization starts, the collagen accumulation diminishes whereas the collagen maturation still continues. This chemical-apposition process in healthy mandibular bone will be used in future as a reference to understand different pathologic conditions that occur in human-mandibular bone.
Topics: Humans; Bone and Bones; Bone Matrix; Osteoblasts; Collagen; Bone Diseases; Calcification, Physiologic
PubMed: 35978052
DOI: 10.1007/s00223-022-01017-4 -
International Journal of Nanomedicine 2021Bone metastasis is one of the common causes of death relative to breast cancer. However, the evolvement of bone niche in cancer progression remains poorly understood. A...
PURPOSE
Bone metastasis is one of the common causes of death relative to breast cancer. However, the evolvement of bone niche in cancer progression remains poorly understood. A three-dimensional (3D) engineered bone matrix was developed as an effective biomimetic model to explore the mechanism relative to bone cancer metastasis.
METHODS
In the study, a 3D engineered bone matrix was developed via cell biomineralization templated by a biomimetic collagen template. The process of bone metastasis relative to breast cancer was investigated by co-culturing breast cancer MDA-MB-231-GFP cells with pre-osteogenic MC3T3-E1 cells on the 3D bone matrix.
RESULTS
A typical bone matrix was obtained, where mineralized collagen fibers were packed into the bundle to form a 3D engineered bone matrix. As the cancer cells were invading along the way vertical to the alignment of mineralized collagen fiber, the bone matrix gradually became thinner, accompanied with the erosion of Col I and the loss of calcium and phosphorus. As a result, the disassembled structure of mineralized collagen fiber was observed, which may be attributed to osteolytic bone metastasis.
CONCLUSION
An engineered 3D bone-like matrix was successfully prepared via cell mineralization, which can act as a model for bone metastasis process. The study revealed mineralized collagen fiber disassembled at nanoscale relative to breast cancer cells.
Topics: Bone Matrix; Bone Neoplasms; Breast Neoplasms; Collagen; Extracellular Matrix; Female; Humans
PubMed: 35002234
DOI: 10.2147/IJN.S338609 -
Journal of Bone and Mineral Research :... Jan 2020Bone fragility fractures are caused by low bone mass or impaired bone quality. Osteoblast/osteoclast coordination determines bone mass, but the factors that control bone...
Bone fragility fractures are caused by low bone mass or impaired bone quality. Osteoblast/osteoclast coordination determines bone mass, but the factors that control bone quality are poorly understood. Osteocytes regulate osteoblast and osteoclast activity on bone surfaces but can also directly reorganize the bone matrix to improve bone quality through perilacunar/canalicular remodeling; however, the molecular mechanisms remain unclear. We previously found that deleting the transcriptional regulators Yes-associated protein (YAP) and transcriptional co-activator with PDZ-motif (TAZ) from osteoblast-lineage cells caused lethality in mice due to skeletal fragility. Here, we tested the hypothesis that YAP and TAZ regulate osteocyte-mediated bone remodeling by conditional ablation of both YAP and TAZ from mouse osteocytes using 8 kb-DMP1-Cre. Osteocyte-conditional YAP/TAZ deletion reduced bone mass and dysregulated matrix collagen content and organization, which together decreased bone mechanical properties. Further, YAP/TAZ deletion impaired osteocyte perilacunar/canalicular remodeling by reducing canalicular network density, length, and branching, as well as perilacunar flourochrome-labeled mineral deposition. Consistent with recent studies identifying TGF-β as a key inducer of osteocyte expression of matrix-remodeling enzymes, YAP/TAZ deletion in vivo decreased osteocyte expression of matrix proteases MMP13, MMP14, and CTSK. In vitro, pharmacologic inhibition of YAP/TAZ transcriptional activity in osteocyte-like cells abrogated TGF-β-induced matrix protease gene expression. Together, these data show that YAP and TAZ control bone matrix accrual, organization, and mechanical properties by regulating osteocyte-mediated bone remodeling. Elucidating the signaling pathways that control perilacunar/canalicular remodeling may enable future therapeutic targeting of bone quality to reverse skeletal fragility. © 2019 American Society for Bone and Mineral Research.
Topics: Animals; Bone Matrix; Bone Remodeling; Mice; Osteoblasts; Osteoclasts; Osteocytes
PubMed: 31610061
DOI: 10.1002/jbmr.3876 -
Acta Orthopaedica Dec 2009Matrix metalloproteinases (MMPs) and related enzymes (ADAMs, ADAMTS) and their inhibitors control matrix turnover and function. Recent advances in our understanding of... (Review)
Review
Matrix metalloproteinases (MMPs) and related enzymes (ADAMs, ADAMTS) and their inhibitors control matrix turnover and function. Recent advances in our understanding of musculoskeletal conditions such as tendinopathy, arthritis, Dupuytren's disease, degenerative disc disease, and bone and soft tissue healing suggest that MMPs have prominant roles. Importantly, MMPs are amenable to inhibition by cheap, safe, and widely available drugs such as the tetracycline antibiotics and the bisphosphonates. This indicates that these MMP inhibitors, if proven effective for any novel indication, may be quickly brought into clinical practice.
Topics: ADAM Proteins; ADAMTS1 Protein; Bone Matrix; Diphosphonates; Humans; Matrix Metalloproteinase Inhibitors; Matrix Metalloproteinases; Musculoskeletal Diseases; Prognosis; Tetracyclines; Treatment Outcome
PubMed: 19968600
DOI: 10.3109/17453670903448257 -
International Journal of Molecular... Jun 2019Wnt signaling plays a pivotal role in maintaining bone mass. Secreted pathway modulators such as sclerostin (SOST) and Dickkopfs (DKKs) may influence bone mass...
Wnt signaling plays a pivotal role in maintaining bone mass. Secreted pathway modulators such as sclerostin (SOST) and Dickkopfs (DKKs) may influence bone mass inhibiting the canonical Wnt pathway. We evaluated whether bone protein content of secreted Wnt antagonists is related to age, bone mass, and strength in postmenopausal osteoporosis. We measured cortical and trabecular bone contents of SOST and Dickkopf-1 (DKK1) in combined extracts obtained after ethylenediaminetetraacetic acid and guanidine hydrochloride extraction in 56 postmenopausal women aged 47-74 (mean, 63) yr with a previous distal forearm fracture and a hip or spine Z-score less than 0. Our findings were (i) SOST and DKK1 protein levels were higher in trabecular bone, (ii) cortical and trabecular DKK1 and trabecular SOST correlated positively with bone matrix levels of osteocalcin ( between 0.28 and 0.45, < 0.05), (iii) cortical DKK1 correlated with lumbar spine bone mineral density (BMD) ( = 0.32, < 0.05) and femoral neck BMD ( = 0.41, < 0.01), and (iv) cortical DKK1 and SOST correlated with apparent bone volumetric density and compressive strength ( between 0.34 and 0.51, < 0.01). In conclusion, cortical bone matrix levels of DKK1 and SOST were positively correlated with bone mass and bone strength in postmenopausal osteoporotic women.
Topics: Adaptor Proteins, Signal Transducing; Aged; Bone Density; Bone Matrix; Bone Morphogenetic Proteins; Female; Genetic Markers; Humans; Intercellular Signaling Peptides and Proteins; Middle Aged; Osteocalcin; Osteoporosis, Postmenopausal
PubMed: 31197079
DOI: 10.3390/ijms20122896 -
The Quarterly Journal of Nuclear... Jun 2019Bone metastases remain a common feature of advanced cancers and are associated with significant morbidity and mortality. Recent research has identified promising novel... (Review)
Review
Bone metastases remain a common feature of advanced cancers and are associated with significant morbidity and mortality. Recent research has identified promising novel treatment targets to improve current treatment strategies for bone metastatic disease. This review summarizes the well-known and recently discovered molecular biology pathways in bone that govern normal physiological remodeling or drive the pathophysiological changes observed when bone metastases are present. In the rapidly changing world of targeted cancer treatments, it is important to recognize the specific treatment effects induced in bone by these agents and the potential impact on common imaging strategies. The osteoclastic targets (bisphosphonates, LGR4, RANKL, mTOR, MET-VEGFR, cathepsin K, Src, Dock 5) and the osteoblastic targets (Wnt and endothelin) are discussed, and the emerging field of osteo-immunity is introduced as potential future therapeutic target. Finally, a summary is provided of available trial data for agents that target these pathways and that have been assessed in patients. The ultimate goal of research into novel pathways and targets involved in the tumor-bone microenvironment is to tackle one of the great remaining unmet needs in oncology, that is finding a cure for bone metastatic disease.
Topics: Animals; Bone Matrix; Bone Neoplasms; Humans; Immunity, Innate; Molecular Targeted Therapy; Osteoclasts; Tumor Microenvironment
PubMed: 31298015
DOI: 10.23736/S1824-4785.19.03203-5 -
Current Osteoporosis Reports Aug 2019Osteocytes are responsible for mechanosensing and mechanotransduction in bone and play a crucial role in bone homeostasis. They are embedded in a calcified collagenous... (Review)
Review
PURPOSE OF REVIEW
Osteocytes are responsible for mechanosensing and mechanotransduction in bone and play a crucial role in bone homeostasis. They are embedded in a calcified collagenous matrix and connected with each other through the lacuno-canalicular network. Due to this specific native environment, it is a challenge to isolate primary osteocytes without losing their specific characteristics in vitro. This review summarizes the commonly used and recently established models to study the function of osteocytes in vitro.
RECENT FINDINGS
Osteocytes are mostly studied in monolayer culture, but recently, 3D models of osteocyte-like cells and primary osteocytes in vitro have been established as well. These models mimic the native environment of osteocytes and show superior osteocyte morphology and behavior, enabling the development of human disease models. Osteocyte-like cell lines as well as primary osteocytes isolated from bone are widely used to study the role of osteocytes in bone homeostasis. Both cells lines and primary cells are cultured in 2D-monolayer and 3D-models. The use of these models and their advantages and shortcomings are discussed in this review.
Topics: Bone Matrix; Cell Line; Culture Techniques; Humans; In Vitro Techniques; Osteocytes; Primary Cell Culture
PubMed: 31240566
DOI: 10.1007/s11914-019-00521-1 -
BioMed Research International 2020Animal tissues and tissue-derived biomaterials are widely used in the field of xenotransplantation and regenerative medicine. A potential immunogenic risk that affects...
BACKGROUND
Animal tissues and tissue-derived biomaterials are widely used in the field of xenotransplantation and regenerative medicine. A potential immunogenic risk that affects the safety and effectiveness of xenografts is the presence of remnant -Gal antigen (synthesized by or/and ). knockout mice have been developed as a suitable model for the analysis of anti-Gal antibody-mediated immunogenicity. However, we are yet to establish whether double knockout (G/i DKO) mice are sensitive to Gal antigen-positive xenoimplants.
METHODS
-Gal antigen expression in the main organs of G/i DKO mice or bovine bone substitutes was detected via a standardized ELISA inhibition assay. Serum anti--Gal antibody titers of G/i DKO mice after immunization with rabbit red blood cells (RRBC) and implantation of raw lyophilized bone substitutes (Gal antigen content was 8.14 ± 3.17 × 10/mg) or Guanhao Biotech bone substitutes (50% decrease in Gal antigen relative to the raw material) were assessed. The evaluation of total serum antibody, inflammatory cytokine, and splenic lymphocyte subtype populations and the histological analysis of implants and thymus were performed to systematically assess the immune response caused by bovine bone substitutes and bone substitute grafts in DKO mice.
RESULTS
-Gal epitope expression was reduced by 100% in the main organs of G/i DKO mice, compared with their wild-type counterparts. Following immunization with RRBC, serum anti-Gal antibody titers of G/i DKO mice increased from 80- to 180-fold. After subcutaneous implantation of raw lyophilized bone substitutes and Guanhao Biotech bone substitutes into G/i DKO mice, specific anti--Gal IgG, anti--Gal IgM, and related inflammatory factors (IFN- and IL-6) were significantly increased in the raw lyophilized bone substitute group but showed limited changes in the Guanhao Biotech bone substitute group, compared with the control.
CONCLUSION
G/i DKO mice are sensitive to Gal antigen-positive xenogeneic grafts and can be effectively utilized for evaluating the -Gal-mediated immunogenic risk of xenogeneic grafts.
Topics: Animals; Bone Matrix; Bone Substitutes; Cattle; Erythrocytes; Galactosyltransferases; Heterografts; Mice; Mice, Knockout; Rabbits; Transplantation, Heterologous; alpha-Galactosidase
PubMed: 32596401
DOI: 10.1155/2020/9680474 -
International Journal of Molecular... Dec 2021Osseointegration is a prerequisite for the long-term success of implants. Titanium implants are preferred for their biocompatibility and mechanical properties....
Osseointegration is a prerequisite for the long-term success of implants. Titanium implants are preferred for their biocompatibility and mechanical properties. Nonetheless, the need for early and immediate loading requires enhancing these properties by adding bioactive coatings. In this preclinical study, extracellular matrix properties and cellular balance at the implant/bone interface was examined. Polyelectrolyte multilayers of chitosan and gelatin or with chitosan and Hyaluronic acid fabricated on titanium alloy using a layer-by-layer self-assembly process were compared with native titanium alloy. The study aimed to histologically evaluate bone parameters that correlate to the biomechanical anchorage enhancement resulted from bioactive coatings of titanium implants in a rat animal model. Superior collagen fiber arrangements and an increased number of active osteocytes reflected a significant improvement of bone matrix quality at the bone interface of the chitosan/gelatin-coated titan implants over chitosan/hyaluronic acid-coated and native implants. Furthermore, the numbers and localization of osteoblasts and osteoclasts in the reparative and remodeling phases suggested a better cellular balance in the chitosan/Gel-coated group over the other two groups. Investigating the micro-mechanical properties of bone tissue at the interface can elucidate detailed discrepancies between different promising bioactive coatings of titanium alloys to maximize their benefit in future medical applications.
Topics: Animals; Biomechanical Phenomena; Bone Matrix; Bone-Implant Interface; Calcification, Physiologic; Coated Materials, Biocompatible; Fibrillar Collagens; Male; Osteoblasts; Osteoclasts; Osteocytes; Rats, Sprague-Dawley; Tibia; Titanium; Rats
PubMed: 35008800
DOI: 10.3390/ijms23010374