Diabetes Mellitus Impairs the Bone Regeneration Capacity of Mesenchymal Stromal Cell-Based Therapy.

Background: Diabetes mellitus (DM) negatively impacts bone tissue, leading to bone loss and increased fracture risk. Many individuals need additional treatments, and therapy based on mesenchymal stromal cells (MSCs) represents a promising treatment for bone defects in patients with diabetes.

Aims: The present study explored the effects of interactions between MSCs from normoglycemic (NG-MSCs) and diabetic (DM-MSCs) donors on osteoblast differentiation and the effects of cell therapy using NG-MSCs on bone regeneration in defects created in diabetic rats.

Agrin-deficient osteocytes disrupt bone tissue homeostasis in male mice.

Osteocytes are terminally differentiated osteoblasts that secrete molecules that regulate bone-tissue homeostasis. Considering that the extracellular matrix protein agrin (AGRN) is secreted by osteoblasts and modulates their differentiation, we hypothesized that AGRN is also expressed by osteocytes and plays a role in their function and therefore in bone remodeling. To test this hypothesis, we deleted agrin specifically in osteocytes using dentin matrix acidic phosphoprotein 1 (DMP1)-Cre mice (C57/BL6 background) and silenced agrin in vitro using clustered regularly interspaced short palindromic repeats/associated nuclease Cas-9 in the Ocy454 osteocyte cell line.

The effect of osteoclasts on epigenetic regulation by long non-coding RNAs in osteoblasts grown on titanium with nanotopography.

Titanium (Ti) implant osseointegration is regulated by the crosstalk among bone cells that are affected by epigenetic machinery, including the regulation of long non-coding RNAs (lncRNAs). Nanotopography Ti (Ti Nano) induces the differentiation of osteoblasts that are inhibited by osteoclasts through epigenetic mechanisms. Thus, we hypothesize that osteoclasts affect lncRNA expression in Ti Nano-cultivated osteoblasts.

Jaboticaba Peel Extract Attenuates Ovariectomy-Induced Bone Loss by Preserving Osteoblast Activity.

Therapies to prevent osteoporosis are relevant since it is one of the most common non-communicable human diseases in the world and the most prevalent bone disorder in adults. Since jaboticaba peel extract (JPE) added to the culture medium enhanced the osteogenic potential of mesenchymal stem cells (MSCs) derived from osteoporotic rats, we hypothesized that JPE prevents the development of ovariectomy-induced osteoporosis. Ovariectomized rats were treated with either JPE (30 mg/kg of body weight) or its vehicle for 90 days, starting 7 days after the ovariectomy.

Efficacy of mesenchymal stem cell-based therapy on the bone repair of hypertensive rats.

Objective: Hypertension disrupts the bone integrity and its repair ability. This study explores the efficiency of a therapy based on the application of mesenchymal stem cells (MSCs) to repair bone defects of spontaneously hypertensive rats (SHR).

Methods: First, we evaluated SHR in terms of bone morphometry and differentiation of MSCs into osteoblasts.

Bone Regeneration and Repair Materials.

Bone tissue has a remarkable ability to regenerate following injury and trauma [...

Mesenchymal stem cell-based therapy for osteoporotic bones: Effects of the interaction between cells from healthy and osteoporotic rats on osteoblast differentiation and bone repair.

Aims: Cell therapy utilizing mesenchymal stem cells (MSCs) from healthy donors (HE-MSCs) is a promising strategy for treating osteoporotic bone defects. This study investigated the effects of interaction between HE-MSCs and MSCs from osteoporotic donors (ORX-MSCs) on osteoblast differentiation of MSCs and of HE-MSCs on bone formation in calvarial defects of osteoporotic rats.

Materials And Methods: Osteoporosis was induced by orchiectomy (ORX) and its effects on the bone were evaluated by femur microtomography (μCT) and osteoblast differentiation of bone marrow MSCs.

Effect of the secretome of mesenchymal stem cells overexpressing BMP-9 on osteoblast differentiation and bone repair.

The secretome present in the conditioned medium (CM) of mesenchymal stem cells (MSCs) is a promising tool to be used in therapies to promote bone regeneration. Considering the high osteogenic potential of the bone morphogenetic protein 9 (BMP-9), we hypothesized that the secretome of MSCs overexpressing BMP-9 (MSCs ) enhances the osteoblast differentiation of MSCs and the bone formation in calvarial defects. CM of either MSCs (CM-MSCs ) or MSCs without BMP-9 overexpression (CM-MSCs ) were obtained at different periods.

Effect of Mesenchymal Stem Cells Overexpressing BMP-9 Primed with Hypoxia on BMP Targets, Osteoblast Differentiation and Bone Repair.

Bone formation is driven by many signaling molecules including bone morphogenetic protein 9 (BMP-9) and hypoxia-inducible factor 1-alpha (HIF-1α). We demonstrated that cell therapy using mesenchymal stem cells (MSCs) overexpressing BMP-9 (MSCs) enhances bone formation in calvarial defects. Here, the effect of hypoxia on BMP components and targets of MSCs and of these hypoxia-primed cells on osteoblast differentiation and bone repair was evaluated.

Effect of osteoblasts on osteoclast differentiation and activity induced by titanium with nanotopography.

Titanium with nanotopography (Ti Nano) favors osteoblast differentiation and attenuates the osteoclast inhibitory effects on osteoblasts. Because the interactions between nanotopography and osteoclasts are underexplored, the aims of this study were to evaluate the effects of Ti Nano on osteoclast differentiation and activity, and the influence of osteoblasts on osteoclast-Ti Nano interaction. The discs were conditioned with a mixture of 10 N HSO and 30% aqueous HO to create Ti Nano and non-conditioned Ti discs were used as control (Ti Control).

Mesenchymal Stem Cells Combined with a P(VDF-TrFE)/BaTiO Scaffold and Photobiomodulation Therapy Enhance Bone Repair in Rat Calvarial Defects.

Background: Tissue engineering and cell therapy have been the focus of investigations on how to treat challenging bone defects. This study aimed to produce and characterize a P(VDF-TrFE)/BaTiO scaffold and evaluate the effect of mesenchymal stem cells (MSCs) combined with this scaffold and photobiomodulation (PBM) on bone repair.

Methods And Results: P(VDF-TrFE)/BaTiO was synthesized using an electrospinning technique and presented physical and chemical properties suitable for bone tissue engineering.

Association of mesenchymal stem cells derived from bone marrow and adipose tissue enhances bone repair in rat calvarial defects.

We evaluated the bone repair induced by MSCs from adipose tissue (AT-MSCs) and bone marrow (BM-MSCs) injected into rat calvarial defects at two time points. Both cell populations expressed MSC surface markers and differentiated into adipocytes and osteoblasts. μCT showed that the combination of cells from distinct sources exhibited synergistic effects to increase bone repair with an advantage when BM-MSCs were injected prior to AT-MSCs.

Effects of Modulation of the Hedgehog and Notch Signaling Pathways on Osteoblast Differentiation Induced by Titanium with Nanotopography.

Background: The events of bone formation and osteoblast/titanium (Ti) interactions may be affected by Hedgehog and Notch signalling pathways. Herein, we investigated the effects of modulation of these signalling pathways on osteoblast differentiation caused by the nanostructured Ti (Ti-Nano) generated by HSO/HO.

Methods: Osteoblasts from newborn rat calvariae were cultured on Ti-Control and Ti-Nano in the presence of the Hedgehog agonist purmorphamine or antagonist cyclopamine and of the Notch antagonist N-(3,5-Difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT) or agonist bexarotene.

Bioactive glass-ceramic for bone tissue engineering: an in vitro and in vivo study focusing on osteoclasts.

Despite the crucial role of osteoclasts in the physiological process of bone repair, most bone tissue engineering strategies have focused on osteoblast-biomaterial interactions. Although Biosilicate® with two crystalline phases (BioS-2P) exhibits osteogenic properties and significant bone formation, its effects on osteoclasts are unknown. This study aimed to investigate the in vitro and in vivo effects of BioS-2P on osteoclast differentiation and activity.

Human periodontal ligament stem cells with distinct osteogenic potential induce bone formation in rat calvaria defects.

This study aimed to evaluate the ability of human periodontal ligament stem cells (PDLSCs) with high (HP-PDLSCs) and low (LP-PDLSCs) osteogenic potential, in addition to mixed cells, to repair bone tissue. Cell phenotype, proliferation and differentiation were evaluated. Undifferentiated PDLSCs were injected into rat calvarial defects and the new bone was evaluated by μCT, histology and real-time PCR.

Photobiomodulation therapy does not depend on the differentiation of dental pulp cells to enhance functional activity associated with angiogenesis and mineralization.

The purpose of this study is to analyze the influence of InGaAlP diode laser (660 nm) with or without an odontogenic medium (OM) in the functional activity of OD-21 cells. Undifferentiated OD-21 pulp cells were cultivated with or without OM and divided into four groups (n = 5): nonirradiated control (C -), nonirradiated + OM (C +), irradiated (L -), and irradiated + OM (L +). Laser application was performed in two sessions of a 24-h interval with an irradiance of 11.

Texturized P(VDF-TrFE)/BT membrane enhances bone neoformation in calvaria defects regardless of the association with photobiomodulation therapy in ovariectomized rats.

Objectives: The purpose of this investigation was to evaluate in vivo the response of bone tissue to photobiomodulation when associated with texturized P(VDF-TrFE)/BT in calvaria defects of ovariectomized rats.

Materials And Methods: Wistar Hannover rats were submitted to ovariectomy/control surgery. Calvaria bone defects of 5-mm diameter were performed after 90 days of ovariectomy.

The extracellular matrix protein Agrin is expressed by osteoblasts and contributes to their differentiation.

The extracellular matrix protein Agrin has been detected in chondrocytes and endosteal osteoblasts but its function in osteoblast differentiation has not been investigated yet. Thus, it is possible that Agrin contributes to osteoblast differentiation and, due to Agrin and wingless-related integration site (Wnt) sharing the same receptor, transmembrane low-density lipoprotein receptor-related protein 4 (Lrp4), and the crosstalk between Wnt and bone morphogenetic protein (BMP) signalling, both pathways could be involved in this Agrin-mediated osteoblast differentiation. Confirming this, Agrin and its receptors Lrp4 and α-dystroglycan (Dag1) were expressed during differentiation of osteoblasts from three different sources.

Miniplates coated by plasma electrolytic oxidation improve bone healing of simulated femoral fractures on low bone mineral density rats.

The treatment of polytrauma patients represents a great challenge in the maxillofacial and orthopedic surgery fields. Therefore, this study tested the hypothesis that the use of a bioactive coating (by plasma electrolytic oxidation, PEO) on titanium microplates could improve the fracture healing of low bone mineral density (BMD) rats. Thirty female rats underwent bilateral ovariectomy surgery (OVX), and 35 rats underwent fake surgery (SHAM).

Green tea extract rich in epigallocatechin gallate impairs alveolar bone loss in ovariectomized rats with experimental periodontal disease.

Periodontal disease and osteoporosis are characterized by bone resorption, and researchers have shown an association between these two diseases through increasing loss of systemic bone mass and triggering alveolar bone loss. Green tea is a common and easily accessible beverage, and evidences show that flavonoid epigallocatechin gallate (EGCG) could decrease bone loss in pathologies such as osteoporosis and periodontal disease. In order to verify its possible effects and apply them in the treatment and prevention of these diseases, this investigation aimed to evaluate the influence of green tea extract (GTE) on bone metabolism of ovariectomized rats after experimental periodontal disease (EPD) by histological, morphological and microtomographic parameters.

Jabuticaba peel extract modulates adipocyte and osteoblast differentiation of MSCs from healthy and osteoporotic rats.

Introduction: The jabuticaba peel extract (JPE) contains bioactive compounds that regulate fat metabolism. Because the negative correlation between fat accumulation and bone formation in bone marrow, we hypothesized that JPE inhibits adipocyte as well as favors osteoblast differentiation of mesenchymal stromal cells (MSCs) under healthy and osteoporotic conditions, a disease that display an imbalance between adipocyte and osteoblast differentiation resulting in reduced bone mass.

Material And Methods: To test these hypotheses, bone marrow MSCs were harvested from healthy and osteoporotic rats and cultured in adipogenic and osteogenic media with three concentrations of JPE, 0.

Frizzled 6 disruption suppresses osteoblast differentiation induced by nanotopography through the canonical Wnt signaling pathway.

This study aimed to investigate if wingless-related integration site (Wnt) signaling participates in the high osteogenic potential of titanium with nanotopography (Ti-Nano). We showed that among the several components of the Wnt signaling pathway, Frizzled 6 (Fzd6) was the transcript most intensely modulated by nanotopography compared with the untreated Ti surface (Ti-Machined). Then, we investigated whether and how Fzd6 participates in the regulation of osteoblast differentiation caused by nanotopography.

Role of embryonic origin on osteogenic potential and bone repair capacity of rat calvarial osteoblasts.

Introduction: The aim of this study was to evaluate the in vitro osteogenic potential of osteoblasts from neural crest-derived frontal bone (OB-NC) and mesoderm-derived parietal bone (OB-MS) and the bone formation induced by them when injected into calvarial defects.

Materials And Methods: Calvarial bones were collected from newborn Wistar rats (3-day old) and characterized as frontal and parietal prior to OB-NC and OB-MS harvesting. The cells were cultured, and several parameters of osteoblast differentiation were evaluated.

Effect of focal adhesion kinase inhibition on osteoblastic cells grown on titanium with different topographies.

Objective: The present study aimed to investigate the participation of focal adhesion kinases (FAK) in interactions between osteoblastic cells and titanium (Ti) surfaces with three different topographies, namely, untreated (US), microstructured (MS), and nanostructured (NS).

Methodology: Osteoblasts harvested from the calvarial bones of 3-day-old rats were cultured on US, MS and NS discs in the presence of PF-573228 (FAK inhibitor) to evaluate osteoblastic differentiation. After 24 h, we evaluated osteoblast morphology and vinculin expression, and on day 10, the following parameters: gene expression of osteoblastic markers and integrin signaling components, FAK protein expression and alkaline phosphatase (ALP) activity.

Inhibitory effects of dabigatran etexilate, a direct thrombin inhibitor, on osteoclasts and osteoblasts.

Introduction: Anticoagulants are widely used in orthopedic surgery to decrease the risk of deep vein thrombosis. While significant bone impairment is induced by long-term heparin therapy, little is known about the effects of direct oral anticoagulants (DOACs). Herein, we investigated the effects of dabigatran etexilate (Pradaxa®), a DOAC inhibitor of thrombin, on bone cells using in vitro and ex vivo cell culture models.