Pyk2 and Megakaryocytes Regulate Osteoblast Differentiation and Migration Via Distinct and Overlapping Mechanisms

Eleniste, Pierre P.; Patel, Vruti; Posritong, Sumana; Zero, Odette; Largura, Heather W.; Cheng, Ying; Himes, Evan R.; Hamilton, Matthew; Baughman, Jenna T.; Kacena, Melissa A.; Bruzzaniti, Angela

doi:10.1002/jcb.25430

Cited by 27 publications

(25 citation statements)

References 51 publications

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“…Osteoblast differentiation is a complex process that involves the process of mesenchymal cells to osteoblasts . It is worth mentioning that osteoblast differentiation is necessary for bone formation during bone remodelling . Moreover, differentiation and activity of osteoblasts and osteoclasts are closely regulated .…”

Section: Discussionmentioning

confidence: 99%

The molecular mechanism study of insulin on proliferation and differentiation of osteoblasts under high glucose conditions

Zhang

Jiang

Bai

et al. 2019

Cell Biochemistry & Function

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To explore the molecular mechanism of insulin on proliferation and differentiation of MC3T3‐E1 cell under high glucose conditions. We first investigated the effect of different concentrations of insulin on the osteoblast cell proliferation and cell differentiation at various time points by MTT analysis, cell cycle analysis, and expression detection of differentiation genes. Then, we used 200 ng/mL of insulin to treat the osteoblast cell at different time points for identifying the common differentially expressed mRNAs among various time points by RNA sequencing. Thirdly, we performed the gene ontology (GO) and the Kyoto Encyclopaedia of Genes and Genomes (KEGG) analysis to explore the biological function of these common differentially expressed mRNAs. The results showed that insulin promoted the cell proliferation and differentiation of osteoblast cell. In RNA sequencing, a total of 31 common differentially expressed mRNAs were identified between different time points. Mt1, Tmem135, Avp, and Dlg2 were found to be associated with the new bone formation. In addition, three important signalling pathways, namely, lysosome, glutamatergic synapse, and chemokine signalling pathways, were found in the KEGG enrichment analysis. Our work demonstrated that insulin could promote the osteoblast cell proliferation and cell differentiation, which may play a key role in bone formation. Significance of the study Our result showed that insulin could promote the proliferation and differentiation of osteoblast at both cellular and molecular levels, which may promote the new bone formation in the osteoblasts.

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Section: Discussionmentioning

confidence: 99%

The molecular mechanism study of insulin on proliferation and differentiation of osteoblasts under high glucose conditions

Zhang

Jiang

Bai

et al. 2019

Cell Biochemistry & Function

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“…Cells were cultured for up to 7 days in osteogenic media to promote osteogenic differentiation and mineral deposition. 39 Osteoblasts on metal plates were fixed with 4% formaldehyde in PBS for 15 minutes. Blocking was performed in 0.1% BSA + 0.05% saponin in PBS for 20 minutes, then labeled for actin with rhodamine phalloidin (Invitrogen, R415) collagen (Chemicon, MAB1330).…”

Section: Characterizationsmentioning

confidence: 99%

“…Cells were imaged using a Leica DMI4000B inverted microscope with attached Retiga digital camera, and using Image Pro software (Media Cybernetics, Inc., Bethesda, MD, USA). 39 Quantitative real-time Pcr (qPcr)…”

Section: Characterizationsmentioning

confidence: 99%

“…qPCR was performed as previously described. 39 Briefly, total RNA was isolated from samples using RNAeasy kit (Qiagen). DNAse I (Thermo-Fisher)-treated RNA was used to generate cDNA by reverse transcription according to the manufacturer's instructions (First Strand cDNA Synthesis Kit; Roche Applied Science).…”

Section: Characterizationsmentioning

confidence: 99%

“…Cells were stained with rhodamine phalloidin (red; Figure 6) which labels filamentous actin (F-actin), a major component of the cellular cytoskeleton. 39 In addition, osteoblasts were stained for collagen type 1 (green).…”

Section: Osteoblast Culturementioning

confidence: 99%

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Enhancement of osteoblast activity on nanostructured NiTi/hydroxyapatite coatings on additive manufactured NiTi metal implants by nanosecond pulsed laser sintering

Deng¹,

Bruzzaniti²,

Cheng³

2018

IJN

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BackgroundThe osteoinductive behaviors of nitinol (NiTi)-based metal implants for bone regeneration are largely dependent on their surface composition and topology. Continuous-mode laser sintering often results in complete melting of the materials and aggregation of particles, which lack control of heat transfer, as well as microstructural changes during sintering of the nanocomposite materials.MethodsIn the current study, in situ direct laser deposition was used to additively manufacture three-dimensional NiTi structures from Ni and Ti powders. The mechanical property of NiTi has been shown to be similar to bone. Nanosecond pulsed laser sintering process was then utilized to generate a nanoporous composite surface with NiTi alloy and hydroxyapatite (HA) by ultrafast laser heating and cooling of Ni, Ti, and HA nanoparticles mixtures precoated on the 3D NiTi substrates; HA was added in order to improve the biocompatibility of the alloy. We then studied the underlying mechanism in the formation of NiTi/HA nanocomposite, and the synergistic effect of the sintered HA component and the nanoporous topology of the composite coating. In addition, we examined the activity of bone-forming osteoblasts on the NiTi/HA surfaces. For this, osteoblast cell morphology and various biomarkers were examined to evaluate cellular activity and function.ResultsWe found that the nanoscale porosity delivered by nanosecond pulsed laser sintering and the HA component positively contributed to osteoblast differentiation, as indicated by an increase in the expression of collagen and alkaline phosphatase, both of which are necessary for osteoblast mineralization. In addition, we observed topological complexities which appeared to boost the activity of osteoblasts, including an increase in actin cytoskeletal structures and adhesion structures.ConclusionThese findings demonstrate that the pulsed laser sintering method is an effective tool to generate biocompatible coatings in complex alloy-composite material systems with desired composition and topology. Our findings also provide a better understanding of the osteoinductive behavior of the sintered nanocomposite coatings for use in orthopedic and bone regeneration applications.

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Lnk Deficiency Leads to TPO-Mediated Osteoclastogenesis and Increased Bone Mass Phenotype

et al. 2017

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The Lnk adapter protein negatively regulates the signaling of thrombopoietin (TPO), the main megakaryocyte (MK) growth factor. Lnk-deficient (−/−) mice have increased TPO signaling and increased MK number. Interestingly, several mouse models exist in which increased MK number leads to a high bone mass phenotype. Here we report the bone phenotype of these mice. MicroCT and static histomorphometric analyses at 20 weeks showed the distal femur of Lnk−/− mice to have significantly higher bone volume fraction and trabecular number compared to wild-type (WT) mice. Notably, despite a significant increase in the number of osteoclasts (OCs), and decreased bone formation rate in Lnk−/− mice compared to WT mice, Lnk−/− mice demonstrated a 2.5-fold greater BV/TV suggesting impaired OC function in vivo. Additionally, Lnk−/− mouse femurs exhibited non-significant increases in mid-shaft cross-sectional area, yet increased periosteal BFR compared to WT femurs was observed. Lnk−/− femurs also had non-significant increases in polar moment of inertia and decreased cortical bone area and thickness, resulting in reduced bone stiffness, modulus, and strength compared to WT femurs. Of note, Lnk is expressed by OC lineage cells and when Lnk−/− OC progenitors are cultured in the presence of TPO, significantly more OCs are observed than in WT cultures. Lnk is also expressed in osteoblast (OB) cells and in vitro reduced alkaline phosphatase activity was observed in Lnk−/− cultures. These data suggest that both direct effects on OB and OC as well as indirect effects of MKs in regulating OB contributes to the observed high bone mass.

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Pyk2 and Megakaryocytes Regulate Osteoblast Differentiation and Migration Via Distinct and Overlapping Mechanisms

Cited by 27 publications

References 51 publications

The molecular mechanism study of insulin on proliferation and differentiation of osteoblasts under high glucose conditions

The molecular mechanism study of insulin on proliferation and differentiation of osteoblasts under high glucose conditions

Enhancement of osteoblast activity on nanostructured NiTi/hydroxyapatite coatings on additive manufactured NiTi metal implants by nanosecond pulsed laser sintering

Lnk Deficiency Leads to TPO-Mediated Osteoclastogenesis and Increased Bone Mass Phenotype

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