Neural crest-derived cells in nasal conchae of adult mice contribute to bone regeneration.

Neural crest-derived cells (NCDCs), a class of adult stem cells not restricted to embryonic tissues, are attractive tissue regenerative therapy candidates because of their ease of isolation, self-renewing properties, and multipotency. Although adult NCDCs can undergo osteogenic differentiation in vitro, whether they induce bone formation in vivo remains unclear. Previously, our group reported findings showing high amounts of NCDCs scattered throughout nasal concha tissues of adult mice. In the present study, NCDCs in nasal conchae labeled with enhanced green fluorescent protein (EGFP) were collected from adult P0-Cre/CAG-CAT-EGFP double transgenic mice, then cultured in serum-free medium to increase the number. Subsequently, NCDCs were harvested and suspended in type I atelocollagen gel, then an atelocollagen sponge was used as a scaffold for the cell suspension. Atelocollagen scaffolds with NCDCs were placed on bone defects created in a mouse calvarial bone defect model. Over the ensuing 12 weeks, micro-CT and histological analysis findings showed that mice with scaffolds containing NCDCs had slightly greater bone formation as compared to those with a scaffold alone. Furthermore, Raman spectroscopy revealed spectral properties of bone in mice that received scaffolds with NCDCs similar to those of native calvarial bone. Bone regeneration is important not only for gaining bone mass but also chemical properties. These results are the first to show the validity of biomolecule-free adult nasal concha-derived NCDCs for bone regeneration, including the chemical properties of regenerated bone tissue.

Nanoindentation time-dependent deformation/recovery suggestive of methylglyoxal induced glycation in calcified nodules.

Although empirical findings have indicated increase in bone fracture risk in type 2 diabetes patients, that has yet to be proven by results obtained at the material level. Here, we report evidence showing nanoscale time-dependent deformation/recovery of in vitro calcified nodules mimicking bone turnover in type 2 diabetes in respect to methylglyoxal (MG)-induced glycation. Nanoindentation test results revealed that calcified nodules cultured with MG did not show adequate dimensional recovery, despite a large creep rate during constant load indentation testing. This lesser recovery is likely based on the linear matrix polymerization network formed by advanced glycation end products (AGEs) as a secondary product of MG. Since elevated serum MG and abnormal bone turnover related to the amount of AGEs are observed in cases of type 2 diabetes, this time-dependent behavior may be one of the factors of the bone fracture mechanism at the material level in affected patients.

[New methods for the evaluation of bone quality. Nanoindentation protocol for measurement of bone mechanical properties of material level.]

Bone is an inhomogeneous, anisotropic natural biomaterial with complex, multiscale structural variations. Thus, experiments on the bulk scale using a universal testing machine are not applicable for localized precision mechanical testing of bone. Nanoscale mechanical testing technologies such as nanoindentation enables to assess the intrinsic toughening mechanism of bone, which is a function of the highly-organized matrix proteins within the mineralized nanostructure. Understanding the basic nanomechanical properties of calcified tissues will help us to appreciate general concepts associated with the excellent design of advanced engineering materials and engineered tissues.

Histomorphometric and histologic evaluation of titanium-zirconium (aTiZr) implants with anodized surfaces.

The choice of implant surface has a significant influence on osseointegration. Modification of TiZr surface by anodization is reported to have the potential to modulate the osteoblast cell behaviour favouring more rapid bone formation. The aim of this study is to investigate the effect of anodizing the surface of TiZr discs with respect to osseointegration after four weeks implantation in sheep femurs. Titanium (Ti) and TiZr discs were anodized in an electrolyte containing DL-α-glycerophosphate and calcium acetate at 300 V. The surface characteristics were analyzed by scanning electron microscopy, electron dispersive spectroscopy, atomic force microscopy and goniometry. Forty implant discs with thickness of 1.5 and 10 mm diameter (10 of each-titanium, titanium-zirconium, anodized titanium and anodized titanium-zirconium) were placed in the femoral condyles of 10 sheep. Histomorphometric and histologic analysis were performed 4 weeks after implantation. The anodized implants displayed hydrophilic, porous, nano-to-micrometer scale roughened surfaces. Energy dispersive spectroscopy analysis revealed calcium and phosphorous incorporation into the surface of both titanium and titanium-zirconium after anodization. Histologically there was new bone apposition on all implanted discs, slightly more pronounced on anodised discs. The percentage bone-to-implant contact measurements of anodized implants were higher than machined/unmodified implants but there was no significant difference between the two groups with anodized surfaces (P > 0.05, n = 10). The present histomorphometric and histological findings confirm that surface modification of titanium-zirconium by anodization is similar to anodised titanium enhances early osseointegration compared to machined implant surfaces.

Spark anodization of titanium-zirconium alloy: surface characterization and bioactivity assessment.

Titanium (Ti) and its alloys have been popularly used as implant biomaterial for decades. Recently, titanium-zirconium (TiZr) alloy has been developed as an alternative implant material with improved strength in load bearing areas. Surface modification is one of the key factors to alter the surface properties to hasten osseointegration. Spark anodic oxidation (anodization) is one such method that is reported to enhance the bone formation around implants. This study aims to anodize TiZr and study its surface characteristics and cytocompatibility by cell culture experiments using osteoblast-like cells. Titanium (Ti) and TiZr discs were anodized in an electrolyte containing DL-α-glycerophosphate and calcium acetate (CA) at 300 V. The surface characteristics were analyzed by scanning electron microscopy, electron dispersive spectroscopy, X-ray diffraction (XRD), atomic force microscopy and goniometry. Using osteoblast-like cells viability, proliferation, differentiation and mineralization was assessed. The anodized surfaces demonstrated increased oxygen, entrapped calcium and phosphorous from the electrolyte used. XRD analysis confirmed the presence of anatase in the oxide layer. Average roughness increased and there was a significant decrease in contact angle (P < 0.01) following anodization. The anodized TiZr (aTiZr) surfaces were more nano-porous compared to anodized Ti (aTi). No significant difference was found in the viability of cells, but after 24 h the total number of cells was significantly higher (P < 0.01). Proliferation, alkaline phosphatase activity and calcium deposits were significantly higher on anodized surfaces compared to machined surfaces (P < 0.05, ANOVA). Anodization of TiZr resulted in a more nanoporous and hydrophilic surface than aTi, and osteoblast biocompatibility appeared comparable to aTi.

Nanomechanical properties and molecular structures of in vitro mineralized tissues on anodically-oxidized titanium surfaces.

The biomechanical stability of mineralized tissues at the interface between implant surface and bone tissue is of critical importance. Anodically oxidized titanium prepared in a chloride solution results in enhanced mineralization of adherent osteoblasts and has antimicrobial activity against oral microorganisms. We evaluated the nanomechanical properties and molecular structures of the in vitro mineralized tissues developing around anodically oxidized titanium surfaces with and without preparation in chloride solution. Anodically oxidized titanium surfaces showed superior osteogenic gene expressions than those of thermally oxidized and bare titanium surfaces. Preparation of anodically oxidized titanium in chloride enhanced the production of mineralized tissue around it. However, the mineralized tissue around anodically oxidized titanium prepared without chloride had increased mineral:matrix and cross-linking ratios, resulting in higher hardness and lower elasticity. FROM THE CLINICAL EDITOR: In this study anodically oxidized titanium was used to enhance the biomechanical stability of mineralized tissues at the implant surface -- bone tissue interface. The mineralized tissue around anodically oxidized titanium prepared without chloride had increased mineral:matrix and cross-linking ratios, resulting in higher hardness and lower elasticity.

A proposed core curriculum for dental English education in Japan.

BACKGROUND: Globalization of the professions has become a necessity among schools and universities across the world. It has affected the medical and dental professions in terms of curriculum design and student and patient needs. In Japan, where medicine and dentistry are taught mainly in the Japanese language, profession-based courses in English, known as Medical English and Dental English, have been integrated into the existing curriculum among its 83 medical and 29 dental schools. Unfortunately, there is neither a core curriculum nor a model syllabus for these courses. METHODS: This report is based on a survey, two discussion forums, a workshop, and finally, the drafting of a proposed core curriculum for dental English approved by consensus of the participants from each university. RESULTS: The core curriculum covers the theoretical aspects, including dental English terms and oral pathologies; and practical aspects, including blended learning and dentist-patient communication. It is divided into modules and is recommended to be offered for at least two semesters. CONCLUSIONS: The core curriculum is expected to guide curriculum developers in schools where dental English courses are yet to be offered or are still in their early development. It may also serve as a model curriculum to medical and dental schools in countries in Asia, Europe, Africa, and Central and South America, where English is not the medium of instruction.

Mechanical insights into jawbone characteristics under chronic kidney disease: A comprehensive nanoindentation approach.

The mechanical properties of the jawbone play a critical role in determining the successful integration of dental prostheses. Chronic kidney disease (CKD) has been identified to abnormally accelerate bone turnover rates. However, the impact of CKD on the mechanical characteristics of the jawbone has not been extensively studied. This study sought to evaluate the time-dependent viscoelastic behaviors of rat jawbones, particularly in the scenarios both with and without CKD. We hypothesized that CKD might compromise the bone's innate toughening mechanisms, potentially owing to the time-dependent viscoelasticity of the bone matrix proteins. The maxillary and mandibular bones of Wistar rats were subjected to nanoindentation and Raman micro-spectroscopy. Load-hold-displacement curves from the cortical regions were obtained via nanoindentation and were mathematically characterized using a suitable viscoelastic constitutive model. Raman micro-spectroscopy was employed to identify nuanced vibrational changes in local molecular structures induced by CKD. The time course of indenter penetration onto cortical bones during the holding stage (creep behavior) can be mathematically represented by a series arrangement of the Kelvin-Voigt bodies. This configuration dictates the overall viscoelastic response observed during nanoindentation tests. The CKD model exhibited a reduced extent of viscoelastic contributions, especially during the initial ramp loading phase in both the maxillary and mandibular cortical bones. The generalized Kelvin-Voigt model comprises 2 K-Voigt elements that signify an immediate short retardation time (τ1) and a subsequent prolonged retardation time (τ2), respectively. Notably, the mandibular CKD model led to an increase in the delayed τ2 alongside an increase in non-enzymatic collagen cross-linking. These suggest that, over time, CKD diminishes the bone's capability for supplementary energy absorption and dimensional recovery, thus heightening their susceptibility to fractures.

Chronic kidney disease compromises structural and mechanical properties of maxillary cortical bone in a rat model.

PURPOSE: This study aimed to investigate the effects of chronic kidney disease (CKD) on the structural and mechanical properties of the maxillary and mandibular cortical bone. METHODS: The maxillary and mandibular cortical bones from CKD model rats were used in this study. CKD-induced histological, structural, and micro-mechanical alterations were assessed using histological analyses, micro-computed tomography (CT), bone mineral density (BMD) measurements, and nanoindentation tests. RESULTS: Histological analyses indicated that CKD caused an increase in the number of osteoclasts and a decrease in the number of osteocytes in the maxilla. Micro-CT analysis revealed that CKD induced a void volume/cortical volume (%) increase, which was more remarkable in the maxilla than in the mandible. CKD also significantly decreased the BMD in the maxilla. In the nanoindentation stress-strain curve, the elastic-plastic transition point and loss modulus were lower in the CKD group than that in the control group in the maxilla, suggesting that CKD increased micro fragility of the maxillary bone. CONCLUSIONS: CKD affected bone turnover in the maxillary cortical bone. Furthermore, the maxillary histological and structural properties were compromised, and micro-mechanical properties, including the elastic-plastic transition point and loss modulus, were altered by CKD.

Lysyl oxidase like-2 reinforces unsatisfactory ossification induced by bone morphogenetic protein-2: relating nanomechanical properties and molecular changes.

Bone morphogenetic protein-2 (BMP2) is among the most popular anabolic agents and substantially increase bone volume related to enhanced osteoblast differentiation. Here we demonstrate a remarkable deterioration in the nanomechanical properties of mineralized tissue induced from osteoblasts solely by the function of BMP2. Mineralized tissue of primary osteoblasts cultured with BMP2 shows molecular features of both bone and cartilage, but depletion of lysyl oxidase family members leads to poor nanomechanical properties of the mineralized tissue. Lysyl oxidase like-2 supplementation reinforces the inferior mineralized tissue induced from osteoblasts by BMP2 through intermolecular cross-linking of type II or type X collagen-rich extracellular matrix. This may also mimic a consolidation of bone fracture gaps, despite the fact that the distribution of the bone properties in such microenvironments has been poorly elucidated. These findings confirm the importance of testing newly induced bone down to the microscale and nanoscale in bone tissue engineering. FROM THE CLINICAL EDITOR: Bone morphogenetic protein-2 is known to substantially increase bone volume related to enhanced osteoblast differentiation; however, this team of investigators report a remarkable deterioration in the nanomechanical properties of mineralized tissue induced from osteoblasts solely by the function of BMP2.

Deciphering load attenuation mechanisms of the dentin-enamel junction: Insights from a viscoelastic constitutive model.

A considerable material discontinuity between the enamel and dentin might jeopardize the tooth's mechanical durability over time without the attenuation of the dentin-enamel junction (DEJ). However, the critical loading transmission mechanism at the DEJ remains understudied. This study aimed to define the extent and effective width of the DEJ, along with its mechanical competence. The presence of DEJ interphase layer was identified using a motif analysis based on the ion beam-transmission electron microscopy coupled with nanoindentation modulus mapping. For each region, nanoindentation load-displacement curves were recorded and mathematically analyzed using an appropriate viscoelastic constitutive model. The time-course of indenter penetration (creep) behavior of the tooth tissues can be mathematically approximated by the Kelvin-Voigt model in series, which determined the visco-contribution to the overall mechanical responses. Therefore, the elastic-plastic contribution can be distinguished from the overall mechanical responses of the tooth after subtracting the visco-contributions. During the loading period, the enamel behavior was dominated by elastic-plastic responses, while both the dentin and DEJ showed pronounced viscoelastic responses. The instantaneous modulus of the DEJ, which was measured by eliminating viscoelastic behavior from the raw load-displacement curve, was almost double that of the dentin. The DEJ was stiffer than the dentin, but it exhibited large viscoelastic motion even at the initial loading stage. This study revealed that the load attenuation competence of the DEJ, which involves extra energy expenditure, is mainly associated with its viscoelasticity. The mathematical analysis proposed here, performed on the nanoindentation creep behavior, could potentially augment the existing knowledge on hard-tissue biomechanics. STATEMENT OF SIGNIFICANCE: In this study, we undertake a rigorous mechanical characterization of the dentin-enamel junction (DEJ) using an advanced nanoindentation technique coupled with a pertinent viscoelastic constitutive model. Our approach unveils the substantial viscoelastic contribution of the DEJ during the initial indentation loading phase and offers an elaborate delineation of the DEJ interphase layer through sophisticated image analysis. These insights significantly augment our understanding of tooth durability. Importantly, our innovative mathematical analysis of creep behavior introduces a novel approach with profound implications for future research in the expansive field of hard-tissue biomechanics. The pioneering methodologies and findings presented in this work hold substantial potential to invigorate progress in biomaterials research and fuel further explorations into the functionality of biological tissues.

Radiographic predictive factors for 10-year survival of removable partial denture abutment teeth: Alveolar bone level and density.

PURPOSE: To determine postoperative periodontal and radiographic factors that predict the survival rates of abutments of removable partial dentures (RPDs). METHODS: Patients who wore RPDs for > 10 years and received supportive periodontal therapy were included. Periodontal examinations and radiographic assessments were conducted on 83 abutment teeth in 35 patients at baseline, and five years after RPD insertion. In addition to conventional factors, such as tooth mobility at 5 years, radiographic factors, such as the crown-root ratio (ΔCR ratio) and gray-level changes reflecting changes in alveolar bone density (ΔABD), were evaluated. The impact of the covariables on the 10-year survival of abutment teeth was estimated using a multivariate Cox regression model, considering multicollinearity. RESULTS: Patients were classified as having A2-B2 (45.7%) and B3-C2 (54.3%) tooth loss, according to the Eichner classification. A probing depth ≥ 4 mm, tooth mobility ≥ grade 1, and CR ratio ≥ 1 were found in 30.1%, 33.7%, and 51.8% of abutment teeth, respectively. The 10-year survival rate of abutment teeth was 86.7%. Multivariate analysis showed that the 10-year survival of abutment teeth was significantly associated with root canal treatment (P = 0.045, hazard ratio [HR] = 1.23), the 5-year ΔCR ratio (P = 0.022, HR = 3.20), and ΔABD on the edentulous side of the abutment teeth (P = 0.047, HR = 1.08). CONCLUSIONS: In addition to root canal treatment, changes in the CR ratio and radiographic alveolar bone density at five years predicted the long-term survival rate of RPD abutments.

Functional non-uniformity of periodontal ligaments tunes mechanobiological stimuli across soft- and hard-tissue interfaces.

The bone-periodontal ligament-tooth (BPT) complex is a unique mechanosensing soft-/hard-tissue interface, which governs the most rapid bony homeostasis in the body responding to external loadings. While the correlation between such loading and alveolar bone remodelling has been widely recognised, it has remained challenging to investigate the transmitted mechanobiological stimuli across such embedded soft-/hard-tissue interfaces of the BPT complex. Here, we propose a framework combining three distinct bioengineering techniques (i, ii, and iii below) to elucidate the innate functional non-uniformity of the PDL in tuning mechanical stimuli to the surrounding alveolar bone. The biphasic PDL mechanical properties measured via nanoindentation, namely the elastic moduli of fibres and ground substance at the sub-tissue level (i), were used as the input parameters in an image-based constitutive modelling framework for finite element simulation (ii). In tandem with U-net deep learning, the Gaussian mixture method enabled the comparison of 5195 possible pseudo-microstructures versus the innate non-uniformity of the PDL (iii). We found that the balance between hydrostatic pressure in PDL and the strain energy in the alveolar bone was maintained within a specific physiological range. The innate PDL microstructure ensures the transduction of favourable mechanobiological stimuli, thereby governing alveolar bone homeostasis. Our outcomes expand current knowledge of the PDL's mechanobiological roles and the proposed framework can be adopted to a broad range of similar soft-/hard- tissue interfaces, which may impact future tissue engineering, regenerative medicine, and evaluating therapeutic strategies. STATEMENT OF SIGNIFICANCE: A combination of cutting-edge technologies, including dynamic nanomechanical testing, high-resolution image-based modelling and machine learning facilitated computing, was used to elucidate the association between the microstructural non-uniformity and biomechanical competence of periodontal ligaments (PDLs). The innate PDL fibre network regulates mechanobiological stimuli, which govern alveolar bone remodelling, in different tissues across the bone-PDL-tooth (BPT) interfaces. These mechanobiological stimuli within the BPT are tuned within a physiological range by the non-uniform microstructure of PDLs, ensuring functional tissue homeostasis. The proposed framework in this study is also applicable for investigating the structure-function relationship in broader types of fibrous soft-/hard- tissue interfaces.

Antimicrobial and osteogenic properties of a hydrophilic-modified nanoscale hydroxyapatite coating on titanium.

Hydroxyapatite (HA)-coated titanium (Ti) is commonly used for implantable medical devices. This study examined in vitro osteoblast gene expression and antimicrobial activity against early and late colonizers of supra-gingival plaque on nanoscale HA-coated Ti prepared by discharge in a physiological buffered solution. The HA-coated Ti surface showed super-hydrophilicity, whereas the densely sintered HA and Ti surfaces alone showed lower hydrophilicity. The sintered HA and HA-coated Ti surfaces enhanced osteoblast phenotypes in comparison with the bare Ti surface. The HA-coated Ti enabled antimicrobial activity against early colonizers of supra-gingival plaques, namely Streptococcus mitis and Streptococcus gordonii. Such antimicrobial activity may be caused by the surface hydrophilicity, thereby leading to a repulsion force between the HA-coated Ti surface and the bacterial cell membranes. On the contrary, the sintered HA sample was susceptible to infection of microorganisms. Thus, hydrophilic-modified HA-coated Ti may have potential for use in implantable medical devices. From the Clinical Editor: This study establishes that Hydroxyapatite (HA)-coated titanium (Ti) surface of implanted devices may result in an optimal microenvironment to control and prevent infections and may have potential future clinical applications.

The structural motifs of mineralized hard tissues from nano- to mesoscale: A future perspective for material science.

Biological tissues have developed structures that fulfil their various specific requirements. Mineralized tissues, such as tooth and bone, are often of mechanical competence for load bearing. Tooth enamel is the hardest and toughest mineralized tissue. Despite a few millimeters thick and with minimal regenerative capacity, human tooth enamel maintains its functions throughout a lifetime. Bone provides skeletal support and essential metabolism to our body. Degenerative diseases and ageing induce the loss of mechanical integrity of the bone, increasing the susceptibility to fractures. Tooth and bone share certain commonalities in chemical components and material characteristics, both consisting of nanocrystalline apatite and matrix proteins as their basic foundational structural units. Although the mechanical properties of such mineralized hard tissues remain unclear, it is plausible that they have an inherent toughening mechanism. Nanoindentation is able to characterize the mechanical properties of tooth enamel and bone at multiscale levels, and the results suggest that such toughening mechanisms of enamel and bone may be mainly associated with the smallest-scale structure-function relationships. These findings will benefit the development of advanced biomaterials in the field of material science and will further our understanding of degenerative bone disease in the clinical community.

Osteocytes in bone aging: Advances, challenges, and future perspectives.

Osteocytes play a critical role in maintaining bone homeostasis and in regulating skeletal response to hormones and mechanical loading. Substantial evidence have demonstrated that osteocytes and their lacunae exhibit morphological changes in aged bone, indicating the underlying involvement of osteocytes in bone aging. Notably, recent studies have deciphered aged osteocytes to have characteristics such as impaired mechanosensitivity, accumulated cellular senescence, dysfunctional perilacunar/canalicular remodeling, and degenerated lacuna-canalicular network. However, detailed molecular mechanisms of osteocytes remain unclear. Nonetheless, osteocyte transcriptomes analyzed via advanced RNA sequencing (RNA-seq) techniques have identified several bone aging-related genes and signaling pathways, such as Wnt, Bmp/TGF, and Jak-STAT. Moreover, inflammation, immune dysfunction, energy shortage, and impaired hormone responses possibly affect osteocytes in age-related bone deterioration. In this review, we summarize the hallmarks of aging bone and osteocytes and discuss osteocytic mechanisms in age-related bone loss and impaired bone quality. Furthermore, we provide insights into the challenges faced and their possible solutions when investigating osteocyte transcriptomes. We also highlight that single-cell RNA-seq can decode transcriptomic messages in aged osteocytes; therefore, this technique can promote novel single cell-based investigations in osteocytes once a well-established standardized protocol specific for osteocytes is developed. Interestingly, improved understanding of osteocytic mechanisms have helped identify promising targets and effective therapies for aging-related osteoporosis and fragile fractures.

Unbiased comparison and modularization identify time-related transcriptomic reprogramming in exercised rat cartilage: Integrated data mining and experimental validation.

Exercise is indispensable for maintaining cartilage integrity in healthy joints and remains a recommendation for knee osteoarthritis. Although the effects of exercise on cartilage have been implied, the detailed mechanisms, such as the effect of exercise time which is important for exercise prescription, remain elusive. In this study, bioinformatic analyses, including unbiased comparisons and modularization, were performed on the transcriptomic data of rat cartilage to identify the time-related genes and signaling pathways. We found that exercise had a notable effect on cartilage transcriptome. Exercise prominently suppressed the genes related to cell division, hypertrophy, catabolism, inflammation, and immune response. The downregulated genes were more prominent and stable over time than the upregulated genes. Although exercise time did not prominently contribute to the effects of exercise, it was a factor related to a batch of cellular functions and signaling pathways, such as extracellular matrix (ECM) homeostasis and cellular response to growth factors and stress. Two clusters of genes, including early and late response genes, were identified according to the expression pattern over time. ECM organization, BMP signaling, and PI3K-Akt signaling were early responsive in the exercise duration. Moreover, time-related signaling pathways, such as inositol phosphate metabolism, nicotinate/nicotinamide metabolism, cell cycle, and Fc epsilon RI signaling pathway, were identified by unbiased mapping and polarization of the highly time-correlated genes. Immunohistochemistry staining showed that Egfr was a late response gene that increased on day 15 of exercise. This study elucidated time-related transcriptomic reprogramming induced by exercise in cartilage, advancing the understanding of cartilage homeostasis.

Identification of mechanics-responsive osteocyte signature in osteoarthritis subchondral bone.

AIMS: Osteoarthritis (OA) is a common degenerative joint disease. The osteocyte transcriptome is highly relevant to osteocyte biology. This study aimed to explore the osteocyte transcriptome in subchondral bone affected by OA. METHODS: Gene expression profiles of OA subchondral bone were used to identify disease-relevant genes and signalling pathways. RNA-sequencing data of a bone loading model were used to identify the loading-responsive gene set. Weighted gene co-expression network analysis (WGCNA) was employed to develop the osteocyte mechanics-responsive gene signature. RESULTS: A group of 77 persistent genes that are highly relevant to extracellular matrix (ECM) biology and bone remodelling signalling were identified in OA subchondral lesions. A loading responsive gene set, including 446 principal genes, was highly enriched in OA medial tibial plateaus compared to lateral tibial plateaus. Of this gene set, a total of 223 genes were identified as the main contributors that were strongly associated with osteocyte functions and signalling pathways, such as ECM modelling, axon guidance, Hippo, Wnt, and transforming growth factor beta (TGF-ß) signalling pathways. We limited the loading-responsive genes obtained via the osteocyte transcriptome signature to identify a subgroup of genes that are highly relevant to osteocytes, as the mechanics-responsive osteocyte signature in OA. Based on WGCNA, we found that this signature was highly co-expressed and identified three clusters, including early, late, and persistently responsive genes. CONCLUSION: In this study, we identified the mechanics-responsive osteocyte signature in OA-lesioned subchondral bone. Cite this article: Bone Joint Res 2022;11(6):362-370.

Knee meniscus regeneration using autogenous injection of uncultured adipose tissue-derived regenerative cells.

Introduction: The low healing potential of mature menisci necessitates traditional surgical removal (meniscectomy) to eliminate acute or chronic degenerative tears. However, removal of meniscal tissue is main factor causing osteoarthritis. Adipose tissue-derived regenerative cells (ADRCs), a heterogeneous cell population that includes multipotent adipose-derived stem cells and other progenitor cells, were easily isolated in large amounts from autologous adipose tissue, and same-day processing without culture or expansion was possible. This study investigated the regenerative potential of autologous ADRCs for use in meniscus defects. Methods: In 10- to 12-week-old male SD rat partial meniscectomy model, an atelocollagen sponge scaffold without or with ADRCs (5.0 × 105 cells) was injected into each meniscus defect. Reconstructed menisci were subjected to histologic, and dynamic mechanical analyses. Results: After 12 weeks, areas of regenerated meniscal tissue in the atelocollagen sponge scaffold in rats with ADRCs (64.54 ± 0.52%, P < 0.05, n = 10) were larger than in those without injection (57.96 ± 0.45%). ADRCs were shown capable of differentiating chondrocyte-like cells and meniscal tissue components such as type II collagen. Higher elastic moduli and lower fluid permeability of regenerated meniscal tissue demonstrated a favorable structure-function relationship required for native menisci, most likely in association with micron-scale porosity, with the lowest level for tissue integrity possibly reproducible. Conclusions: This is the first report of meniscus regeneration induced by injection of ADRCs. The results indicate that ADRCs will be useful in future clinical cell-based therapy strategies, including as a cell source for reconstruction of damaged knee menisci.

Long-term observation of periodontal condition following placement of removable partial dentures with rigid retainers and major connector in patients with/without diabetes: A retrospective study.

PURPOSE: This retrospective study evaluated the periodontal tissues of the abutment teeth of removable partial dentures (RPDs) with rigid retainers and major connectors in patients with and without type 2 diabetes mellitus (T2D). METHODS: A total of 313 patients who had been treated with RPDs, including rigid retainers and major connectors, were divided into two groups: T2D and non-T2D. The periodontal parameters and radiographic bone heights of the abutment teeth were evaluated at baseline and at a 5-year examination during supportive periodontal therapy (SPT). For patients with accessible standardized radiographs, bone density was analyzed based on the gray level (GL) using digital subtraction radiography (n = 83). RESULTS: Overall, 739 abutment teeth (86 in the T2D group) of 235 patients (25 in the T2D group) were analyzed, and 95.0% (94.2% in the T2D group, and 95.2% in the non-T2D group) were maintained. The mean probing pocket depth significantly increased in both groups (p < 0.001). There were significant changes in the radiographic bone height (p = 0.038) and GL on the side of the denture base area (p = 0.048) in the T2D group compared to those in the non-T2D group. CONCLUSION: Regardless of T2D, RPDs with rigid retainers and major connectors could prevent the progression of periodontal disease and successfully maintain most of the abutment teeth during 5-years of SPT. However, T2D may be significantly associated with loss of bone height reduction and density on the side of the denture base area.