Nell-1 Enhances Osteogenic Differentiation of Pre-Osteoblasts on Titanium Surfaces via the MAPK-ERK Signaling Pathway

Shen, Meijie; Wang, Gege; Wang, Yuzhen; Xie, Jing; Ding, Xi

doi:10.1159/000494651

Cited by 22 publications

(18 citation statements)

References 44 publications

(31 reference statements)

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“…Therefore, we elucidated the MAPK/ERK signaling pathway underlying the effects of DA on BMSC osteogenic differentiation. Interestingly, the results showed that the D1 receptor agonist selectively activated ERK rather than the JNK and P38 pathways in BMSCs, and different cell types might have influences on this activity [42].…”

Section: Discussionmentioning

confidence: 99%

Dopamine D1 receptor-mediated activation of the ERK signaling pathway is involved in the osteogenic differentiation of bone mesenchymal stem cells

Wang

et al. 2020

Stem Cell Res Ther

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BackgroundOsteogenic differentiation of bone mesenchymal stem cells (BMSCs) is regulated by numerous signaling pathways. Dopamine (DA), a neurotransmitter, has previously been demonstrated to induce new bone formation by stimulating the receptors on BMSCs, but the essential mediators of DA-induced osteogenic signaling remain unclear.MethodsIn this work, we evaluated the influence of both dopamine D1 and D2 receptor activation on BMSC osteogenic differentiation. Gene and protein expression of osteogenic-related markers were tested. The direct binding of transcriptional factor, Runx2, to those markers was also investigated. Additionally, cellular differentiation-associated signaling pathways were evaluated.ResultsWe showed that the expression level of the D1 receptor on BMSCs increased during osteogenic differentiation. A D1 receptor agonist, similar to DA, induced the osteogenic differentiation of BMSCs, and this phenomenon was effectively inhibited by a D1 receptor antagonist or by D1 receptor knockdown. Furthermore, the suppression of protein kinase A (PKA), an important kinase downstream of the D1 receptor, successfully inhibited DA-induced BMSC osteogenic differentiation and decreased the phosphorylation of ERK1/2. Compared with P38, MAPK, and JNK, DA mainly induced the phosphorylation of ERK1/2 and led to the upregulation of Runx2 transcriptional activity, thus facilitating BMSC osteogenic differentiation. On the other hand, an ERK1/2 inhibitor could reverse these effects.ConclusionsTaken together, these results suggest that ERK signaling may play an essential role in coordinating the DA-induced osteogenic differentiation of BMSCs by D1 receptor activation.

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Section: Discussionmentioning

confidence: 99%

Dopamine D1 receptor-mediated activation of the ERK signaling pathway is involved in the osteogenic differentiation of bone mesenchymal stem cells

Wang

et al. 2020

Stem Cell Res Ther

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“…Protein kinase C-binding protein, also known as NELlike protein 1 (NELL1) or Nel-related protein 1, was identified for hand OA in our study. The important role of NELL-1 in driving differentiation and growth of bone and cartilage tissue has been well documented in recent years (25). A recent study showed that adding NELL1 to the human perivascular stem cells (hPSCs) could increase the gene and protein expression of chondrogenic markers, suggesting the role of NELL1 in enhancing and accelerating cartilage repair (26).…”

Section: Discussionmentioning

confidence: 99%

Assessing the genetic relationships between osteoarthritis and human plasma proteins: a large scale genetic correlation scan

et al. 2020

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Background: Osteoarthritis (OA) is a multifactorial complex disease. The impact of plasma proteins on OA remains elusive now. Methods:The UK Biobank genome-wide association study data of OA was used here. Genome-wide SNP genotyping was performed using the Affymetrix UK BiLEVE Axiom or UK Biobank Axiom array.Equally, the GWAS summary data of 3,622 plasma proteins was derived from a recently published study.Consequently, linkage disequilibrium score regression (LD score regression) analysis was performed to evaluate the genetic correlation between each plasma protein and different sites of OA.Results: Several suggestive plasma proteins were identified for OA. For hand OA, evidence of genetic correlation was observed for inter-alpha-trypsin inhibitor heavy chain H1 (coefficient =−0.3854, P value =0.0198), multiple inositol polyphosphate phosphatase 1 (coefficient =−1.1721, P value =0.0303). For hip OA, 7 suggestive genetic correlation signals were observed, such as Transmembrane glycoprotein NMB (coefficient =0.6944, P value =0.0098), Endothelial cell-specific molecule 1 (coefficient =0.6337, P value =0.03). For Knee OA, 12 suggestive genetic correlation signals were identified, including Elafin (coefficient =−0.5562, P value =0.0092), Interleukin-16 (coefficient =0.3949, P value =0.0435). Conclusions:We investigated the genetic correlations between plasma proteins and different sites of OA in a systematic way. Our results provide novel evidence that OA is a heterogeneous disease.

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“…SPARC-related modular calcium binding 1 has been revealed to be closely involved in osteogenic differentiation of BMSCs and has the potential to promote bone regeneration in vivo [28]. It has been suggested that the MAPK/ERK signaling pathways may be related to the Nell-1 induced osteogenic differentiation of pre-osteoblasts on titanium surfaces [29]. ERK1/2, p38 MAPK, and JNK osteogenic signaling pathways have been demonstrated to participate in mechanical stress-induced osteoblastic differentiation [30].…”

Section: Discussionmentioning

confidence: 99%

Silencing of SPARC represses heterotopic ossification via inhibition of the MAPK signaling pathway

et al. 2019

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Heterotopic ossification (HO), the pathologic formation of extraskeletal bone, can be disabling and lethal. However, the underlying molecular mechanisms were largely unknown. The present study aimed to clarify the involvement of secreted protein acidic and rich in cysteine (SPARC) and the underlying mechanism in rat model of HO. The mechanistic investigation on roles of SPARC in HO was examined through gain- and loss-of-function approaches of SPARC, with alkaline-phosphatase (ALP) activity, mineralized nodules, and osteocalcin (OCN) content measured. To further confirm the regulatory role of SPARC, levels of mitogen-activated protein kinase (MAPK) signaling pathways-related proteins (extracellular signal-regulated kinase (ERK), c-jun N-terminal kinase (JNK), p38, nuclear factor κ-B (NF-κB), and IkB kinase β (IKKβ)) were determined. Bone marrow mesenchymal stem cells were treated with pathway inhibitor to investigate the relationship among SPARC, MAPK signaling pathway, and HO. The results suggested that SPARC expression was up-regulated in Achilles tendon tissues of HO rats. Silencing of SPARC could decrease phosphorylation of ERK, JNK, p38, NF-κB, and IKKβ. Additionally, silencing of SPARC or inhibition of MAPK signaling pathway could reduce the ALP activity, the number of mineralized nodules, and OCN content, thus impeding HO. To sum up, our study identifies the inhibitory role of SPARC gene silencing in HO via the MAPK signaling pathway, suggesting SPARC presents a potential target for HO therapy.

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Nell-1 Enhances Osteogenic Differentiation of Pre-Osteoblasts on Titanium Surfaces via the MAPK-ERK Signaling Pathway

Cited by 22 publications

References 44 publications

Dopamine D1 receptor-mediated activation of the ERK signaling pathway is involved in the osteogenic differentiation of bone mesenchymal stem cells

Dopamine D1 receptor-mediated activation of the ERK signaling pathway is involved in the osteogenic differentiation of bone mesenchymal stem cells

Assessing the genetic relationships between osteoarthritis and human plasma proteins: a large scale genetic correlation scan

Silencing of SPARC represses heterotopic ossification via inhibition of the MAPK signaling pathway

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