scholarly journals Dmp1 Lineage Cells Contribute Significantly to Periosteal Lamellar Bone Formation Induced by Mechanical Loading but Are Depleted from The Bone Surface During Rapid Bone Formation

JBMR Plus ◽  
2021 ◽  
Author(s):  
Taylor L. Harris ◽  
Matthew J. Silva
Keyword(s):  
Bone Formation ◽  
Mechanical Loading ◽  
Lamellar Bone ◽  
Bone Surface

scholarly journals Nitric oxide-mediated vasodilation increases blood flow during the early stages of stress fracture healing

2014 ◽  
Vol 116 (4) ◽  
pp. 416-424 ◽  
Author(s):  
Ryan E. Tomlinson ◽  
Kooresh I. Shoghi ◽  
Matthew J. Silva
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Bone Formation ◽  
Mechanical Loading ◽  
Stress Fracture ◽  
Flow Rate ◽  
Vascular Function ◽  
Blood Flow Rate ◽  
Lamellar Bone ◽  
Woven Bone

Despite the strong connection between angiogenesis and osteogenesis in skeletal repair conditions such as fracture and distraction osteogenesis, little is known about the vascular requirements for bone formation after repetitive mechanical loading. Here, established protocols of damaging (stress fracture) and nondamaging (physiological) forelimb loading in the adult rat were used to stimulate either woven or lamellar bone formation, respectively. Positron emission tomography was used to evaluate blood flow and fluoride kinetics at the site of bone formation. In the group that received damaging mechanical loading leading to woven bone formation (WBF),15O water (blood) flow rate was significantly increased on day 0 and remained elevated 14 days after loading, whereas18F fluoride uptake peaked 7 days after loading. In the group that received nondamaging mechanical loading leading to lamellar bone formation (LBF),15O water and18F fluoride flow rates in loaded limbs were not significantly different from nonloaded limbs at any time point. The early increase in blood flow rate after WBF loading was associated with local vasodilation. In addition, Nos2 expression in mast cells was increased in WBF-, but not LBF-, loaded limbs. The nitric oxide (NO) synthase inhibitor Nω-nitro-l-arginine methyl ester was used to suppress NO generation, resulting in significant decreases in early blood flow rate and bone formation after WBF loading. These results demonstrate that NO-mediated vasodilation is a key feature of the normal response to stress fracture and precedes woven bone formation. Therefore, patients with impaired vascular function may heal stress fractures more slowly than expected.

scholarly journals Antagonizing the αvβ3Integrin Inhibits Angiogenesis and Impairs Woven but Not Lamellar Bone Formation Induced by Mechanical Loading

2014 ◽  
Vol 29 (9) ◽  
pp. 1970-1980 ◽  
Author(s):  
Ryan E Tomlinson ◽  
Anne H Schmieder ◽  
James D Quirk ◽  
Gregory M Lanza ◽  
Matthew J Silva
Keyword(s):  
Bone Formation ◽  
Mechanical Loading ◽  
Lamellar Bone

scholarly journals Regeneration in Experimental Alveolar Bone Defect Using Human Umbilical Cord Mesenchymal Stem Cells

2021 ◽  
Vol 30 ◽  
pp. 096368972097539
Author(s):  
Akiko Toyota ◽  
Rei Shinagawa ◽  
Mikiko Mano ◽  
Kazuyuki Tokioka ◽  
Naoto Suda
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Bone Formation ◽  
Cleft Lip ◽  
Human Umbilical Cord ◽  
Bone Surface ◽  
Bone Bridge ◽  
Bridge Formation ◽  
Alveolar Cleft ◽  
Umbilical Cords

Cleft lip and palate is a congenital disorder including cleft lip, and/or cleft palate, and/or alveolar cleft, with high incidence.The alveolar cleft causes morphological and functional abnormalities. To obtain bone bridge formation and continuous structure between alveolar clefts, surgical interventions are performed from infancy to childhood. However, desirable bone bridge formation is not obtained in many cases. Regenerative medicine using mesenchymal stem cells (MSCs) is expected to be a useful strategy to obtain sufficient bone bridge formation between alveolar clefts. In this study, we examined the effect of human umbilical cord-derived MSCs by transplantation into a rat experimental alveolar cleft model. Human umbilical cords were digested enzymatically and the isolated cells were collected (UC-EZ cells). Next, CD146-positive cells were enriched from UC-EZ cells by magnetic-activated cell sorting (UC-MACS cells). UC-EZ and UC-MACS cells showed MSC gene/protein expression, in vitro. Both cells had multipotency and could differentiate to osteogenic, chondrogenic, and adipogenic lineages under the differentiation-inducing media. However, UC-EZ cells lacked Sox2 expression and showed the lower ratio of MSCs than UC-MACS cells. Thus, UC-MACS cells were transplanted with hydroxyapatite and collagen (HA + Col) into alveolar cleft model to evaluate bone formation in vivo. The results of micro computed tomography and histological staining showed that UC-MACS cells with HA + Col induced more abundant bone formation between the experimental alveolar clefts than HA + Col implantation only. Cells immunopositive for osteopontin were accumulated along the bone surface and some of them were embedded in the bone. Cells immunopositive for human-specific mitochondria were aligned along the newly formed bone surface and in the new bone, suggesting that UC-MACS cells contributed to the bone bridge formation between alveolar clefts. These findings indicate that human umbilical cords are reliable bioresource and UC-MACS cells are useful for the alveolar cleft regeneration.

scholarly journals Conditional Deletion of Prolyl Hydroxylase Domain-Containing Protein 2 (Phd2) Gene Reveals Its Essential Role in Chondrocyte Function and Endochondral Bone Formation

Endocrinology ◽  
2016 ◽  
Vol 157 (1) ◽  
pp. 127-140 ◽  
Author(s):  
Shaohong Cheng ◽  
Weirong Xing ◽  
Sheila Pourteymoor ◽  
Jan Schulte ◽  
Subburaman Mohan
Keyword(s):  
Bone Formation ◽  
Growth Plate ◽  
Prolyl Hydroxylase ◽  
Conditional Knockout ◽  
Hypertrophic Chondrocytes ◽  
Endochondral Bone Formation ◽  
Bone Surface ◽  
Endochondral Bone ◽  
Prolyl Hydroxylase Domain

Abstract The hypoxic growth plate cartilage requires hypoxia-inducible factor (HIF)-mediated pathways to maintain chondrocyte survival and differentiation. HIF proteins are tightly regulated by prolyl hydroxylase domain-containing protein 2 (Phd2)-mediated proteosomal degradation. We conditionally disrupted the Phd2 gene in chondrocytes by crossing Phd2 floxed mice with type 2 collagen-α1-Cre transgenic mice and found massive increases (>50%) in the trabecular bone mass of long bones and lumbar vertebra of the Phd2 conditional knockout (cKO) mice caused by significant increases in trabecular number and thickness and reductions in trabecular separation. Cortical thickness and tissue mineral density at the femoral middiaphysis of the cKO mice were also significantly increased. Dynamic histomorphometric analyses revealed increased longitudinal length and osteoid surface per bone surface in the primary spongiosa of the cKO mice, suggesting elevated conversion rate from hypertrophic chondrocytes to mineralized bone matrix as well as increased bone formation in the primary spongiosa. In the secondary spongiosa, bone formation measured by mineralizing surface per bone surface and mineral apposition rate were not changed, but resorption was slightly reduced. Increases in the mRNA levels of SRY (sex determining region Y)-box 9, osterix (Osx), type 2 collagen, aggrecan, alkaline phosphatase, bone sialoprotein, vascular endothelial growth factor, erythropoietin, and glycolytic enzymes in the growth plate of cKO mice were detected by quantitative RT-PCR. Immunohistochemistry revealed an increased HIF-1α protein level in the hypertrophic chondrocytes of cKO mice. Infection of chondrocytes isolated from Phd2 floxed mice with adenoviral Cre resulted in similar gene expression patterns as observed in the cKO growth plate chondrocytes. Our findings indicate that Phd2 suppresses endochondral bone formation, in part, via HIF-dependent mechanisms in mice.

scholarly journals A Delphinidin-Enriched Maqui Berry Extract Improves Bone Metabolism and Protects against Bone Loss in Osteopenic Mouse Models

Antioxidants ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 386 ◽  
Author(s):  
Masahiro Nagaoka ◽  
Toyonobu Maeda ◽  
Masahiro Chatani ◽  
Kazuaki Handa ◽  
Tomoyuki Yamakawa ◽  
...  
Keyword(s):  
Bone Loss ◽  
Bone Formation ◽  
Bone Metabolism ◽  
Mouse Models ◽  
Bone Morphogenetic Protein 2 ◽  
Bone Surface ◽  
Bone Formation Rate ◽  
Trabecular Thickness ◽  
Tissue Volume ◽  
Maqui Berry

In our previous investigation, delphinidin, one of the most abundant anthocyanins found in vegetables and berry fruits, had been shown to inhibit osteoclasts and prevent bone loss in mouse models of osteoporosis. In the present study, we investigated whether a delphinidin glycoside-enriched maqui berry extract (MBE, Delphinol®) exhibits beneficial effects on bone metabolism both in vitro and in vivo. MBE stimulated the osteoblastic differentiation of MC3T3-E1 cells, as indicated by enhanced mineralized nodule formation, and increased alkaline phosphatase activity, through the upregulation of bone morphogenetic protein 2 (Bmp2), runt-related transcription factor 2 (Runx2), Osterix (Osx), osteocalcin (Ocn), and matrix extracellular phosphoglycoprotein (Mepe) mRNA expression. Immunostaining and immunoprecipitation assays demonstrated that MBE suppressed NF-κB transnucleation through acting as a superoxide anion/peroxynitrite scavenger in MC3T3-E1 cells. Simultaneously, MBE inhibited both osteoclastogenesis in primary bone marrow macrophages and pit formation by maturated osteoclasts on dentine slices. Microcomputed tomography (micro-CT) and bone histomorphometry analyses of femurs demonstrated that the daily ingestion of MBE significantly increased BV/TV (ratio of bone volume to tissue volume), Tb.Th (trabecular thickness), Tb.N (trabecular number), N.Nd/N.Tm (node to terminus ratio), OV/TV (ratio of osteoid volume to tissue volume), BFR/TV (bone formation rate per tissue volume), and significantly decreased Tb.Sp (trabecular separation), ES/BS (ratio of eroded surface to bone surface) and N.Oc/BS (number of osteoclast per unit of bone surface), compared to vehicle controls in osteopenic mouse models. These findings suggest that MBE can be a promising natural agent for the prevention of bone loss in osteopenic conditions by not only inhibiting bone resorption, but also stimulating bone formation.

scholarly journals Effect of mechanical loading on insulin-like growth factor-I gene expression in rat tibia

2007 ◽  
Vol 192 (1) ◽  
pp. 131-140 ◽  
Author(s):  
Christianne M A Reijnders ◽  
Nathalie Bravenboer ◽  
Annechien M Tromp ◽  
Marinus A Blankenstein ◽  
Paul Lips
Keyword(s):  
Bone Formation ◽  
Mrna Expression ◽  
Mechanical Loading ◽  
Mechanical Stimulation ◽  
Molecular Mechanisms ◽  
Bone Marrow Cells ◽  
Mechanical Stimuli ◽  
Igf I ◽  
Female Wistar Rats ◽  
Tibia Shaft

Mechanical loading plays an essential role in maintaining skeletal integrity. Mechanical stimulation leads to increased bone formation. However, the cellular and molecular mechanisms that are involved in the translation of mechanical stimuli into bone formation, are not completely understood. Growth factors and osteocytes, which act as mechanosensors, play a key role during the bone formation after mechanical stimulation. The aim of this study was to characterize the role of IGF-I in the translation of mechanical stimuli into bone formation locally in rat tibiae. Fifteen female Wistar rats were randomly assigned to three groups (n = 5): load, sham-loaded, and control. The four-point bending model of Forwood and Turner was used to induce a single period of mechanical loading on the tibia shaft. The effects of mechanical loading on IGF-I mRNA expression were determined with non-radioactive in situ hybridization on decalcified tibiae sections, 6 h after the loading session. Endogenous IGF-I mRNA was expressed in trabecular and cortical osteoblasts, some trabecular and sub-endocortical osteocytes, intracortical endothelial cells of blood vessels, and periosteum. Megakaryocytes, macrophages, and myeloid cells also expressed IGF-I mRNA. In the growth plate, IGF-I mRNA was located in proliferative and hypertrophic chondrocytes. Mechanical loading did not affect the IGF-I mRNA expression in osteoblasts, bone marrow cells, and chondrocytes, but the osteocytes at the endosteal side of the shaft showed a twofold increase of IGF-I mRNA expression. The proportion of IGF-I mRNA positive osteocytes in loaded tibiae was 29.3 ± 12.9% (mean ± s.d.; n = 5), whereas sham-loaded and contra-lateral control tibiae exhibited 16.7 ± 4.4% (n = 5) and 14.7 ± 4.2% (n = 10) respectively (P < 0.05). Lamellar bone formation after a single mechanical loading session was observed at the endosteal side of the shaft. In conclusion, a single loading session results in a twofold up-regulation of IGF-I mRNA synthesis in osteocytes which are present in multiple layers extending into the cortical bone of mechanically stimulated tibia shaft 6 h after loading. This supports the hypothesis that IGF-I, which is located in osteocytes, is involved in the translation of mechanical stimuli into bone formation.

Osteoblast/osteocyte-derived interleukin-11 regulates osteogenesis and systemic adipogenesis

2021 ◽  
Author(s):  
Bingzi Dong ◽  
Masahiro Hiasa ◽  
Itsuro Endo ◽  
Yukiyo Ohnishi ◽  
Takeshi Kondo ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Adipose Tissue ◽  
Bone Formation ◽  
Mechanical Loading ◽  
Therapeutic Approaches ◽  
New Therapeutic Approaches ◽  
Mechanical Unloading ◽  
Enhanced Expression ◽  
Wnt Inhibitors ◽  
Interleukin 11

Abstract Exercise offers mechanical loading to the bone, while it stimulates energy expenditure in the adipose tissue. Thus, bone may secrete a factor to communicate with adipose tissue in response to mechanical loading. Interleukin (IL)-11 is expressed in the bone, upregulated by mechanical loading, enhances osteogenesis and suppresses adipogenesis. Systemic IL-11 deletion (IL-11−/−) exhibited reduced bone mass, suppressed bone formation response to mechanical loading, enhanced expression of Wnt inhibitors, and suppressed Wnt signaling. Enhancement of bone resorption under mechanical unloading was unaffected. Unexpectedly, IL-11−/− mice showed increased systemic adiposity and glucose intolerance. Osteoblast/osteocyte-specific IL-11 deletion in osteocalcin-Cre;IL-11fl/fl mice showed reduced serum IL-11, blunted bone formation under mechanical loading, and increased systemic adiposity similar to IL-11−/− mice. Adipocyte-specific IL-11 deletion in adiponectin-Cre; IL-11fl/fl mice exhibited no abnormality. Thus, IL-11 from osteoblast/osteocyte controls both osteogenesis and systemic adiposity in response to mechanical loading. These findings may bring new therapeutic approaches to osteoporosis and metabolic syndrome.

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