Role of the unfolded protein response in topography-induced osteogenic differentiation in rat bone marrow mesenchymal stem cells

Shi, Minmin; Song, Wen; Han, Tianxiao; Chang, Bei; Li, Guangwen; Jin, Jianfeng; Zhang, Yumei

doi:10.1016/j.actbio.2017.03.018

Cited by 28 publications

(30 citation statements)

References 44 publications

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“…Through inserting the implants with different topographies into the femurs of mice and the consequent histological analysis and mechanical detection, the osteogenesis was NT-30. NT-100.P, which is partly different from our in vitro results and the studies in vitro performed by Zhao et al 26 and Shi et al 29 The differences between in vitro and in vivo in our studies might even be related to the osteogenic environment influenced by the topography of Ti implants. Macrophages play quite vital roles in the prognosis of implantation,…”

Section: Discussioncontrasting

confidence: 99%

Nanostructured titanium regulates osseointegration via influencing macrophage polarization in the osteogenic environment

Wang¹,

Meng²,

Song³

et al. 2018

IJN

Self Cite

101

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IntroductionFabricating nanostructured surface topography represents the mainstream approach to induce osteogenesis for the next-generation bone implant. In the past, the bone implant was designed to minimize host repulsive reactions in order to acquire biocompatibility. However, increasing reports indicate that the absence of an appropriate immune response cannot acquire adequate osseointegration after implantation in vivo.Materials and methodsWe prepared different topographies on the surface of titanium (Ti) specimens by grinding, etching and anodizing, and they were marked as polished specimen (P), specimen with nanotubes (NTs) in small diameters (NT-30) and specimen with NTs in large diameters (NT-100). We evaluated the ability of different topographies of the specimen to induce osteogenic differentiation of mice bone marrow mesenchymal stem cells (BMSCs) in vitro and to induce osseointegration in vivo. Furthermore, we investigated the effect of different topographies on the polarization and secretion of macrophages, and the effect of macrophage polarization on topography-induced osteogenic differentiation of mice BMSCs. Finally, we verified the effect of macrophage polarization on topography-induced osseointegration in vivo by using Cre*RBP-Jfl/fl mice in which classically activated macrophage was restrained.ResultsThe osteogenic differentiation of mice BMSCs induced by specimen with different topographies was NT-100>NT-30>P, while the osseointegration induced by specimen with different topographies in vivo was NT-30>NT-100>P. In addition, specimen of NT-30 could induce more macrophages to M2 polarization, while specimen of P and NT-100 could induce more macrophages to M1 polarization. When co-culture mice BMSCs and macrophages on specimen with different topographies, the osteogenic differentiation of mice BMSCs was NT-30>NT-100≥P. The osseointegration induced by NT-100 in Cre*RBP-Jfl/fl mice was much better than that of wild type mice.ConclusionIt is suggested that the intrinsic immunomodulatory effects of nanomaterials are not only crucial to evaluate the in vivo biocompatibility but also required to determine the final osseointegration. To clarify the immune response and osseointegration may be beneficial for the designation and optimization of the bone implant.

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Section: Discussioncontrasting

confidence: 99%

Nanostructured titanium regulates osseointegration via influencing macrophage polarization in the osteogenic environment

Wang¹,

Meng²,

Song³

et al. 2018

IJN

Self Cite

101

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“…TUDCA has been shown to attenuate ER stress and prevent UPR dysfunction through prevention of Grp78/BiP upregulation, suppression of PERK and JNK phosphorylation, and prohibition of the expression of CHOP (Malo et al, ). In vitro, TUDCA was shown to enhance osteogenic differentiation of BM‐MSCs (Cha et al, ; Han et al, ; Shi et al, ) and suppress the adipogenic differentiation of ADSCs (Cha et al, ). Here, we found that although TUDCA was very effective in increasing osteogenic differentiation, and to a lesser extent adipogenic differentiation, its effects were mainly visible as a normalization of the UPR.…”

Section: Discussionmentioning

confidence: 99%

Bone marrow mesenchymal stem cell donors with a high body mass index display elevated endoplasmic reticulum stress and are functionally impaired

Ulum

Teker

Sarıkaya

et al. 2018

Journal Cellular Physiology

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Bone marrow mesenchymal stem cells (BM-MSCs) are promising candidates for regenerative medicine purposes. The effect of obesity on the function of BM-MSCs is currently unknown. Here, we assessed how obesity affects the function of BM-MSCs and the role of endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) therein. BM-MSCs were obtained from healthy donors with a normal (<25) or high (>30) body mass index (BMI). High-BMI BM-MSCs displayed severely impaired osteogenic and diminished adipogenic differentiation, decreased proliferation rates, increased senescence, and elevated expression of ER stress-related genes ATF4 and CHOP. Suppression of ER stress using tauroursodeoxycholic acid (TUDCA) and 4-phenylbutyrate (4-PBA) resulted in partial recovery of osteogenic differentiation capacity, with a significant increase in the expression of ALPL and improvement in the UPR. These data indicate that BMI is important during the selection of BM-MSC donors for regenerative medicine purposes and that application of high-BMI BM-MSCs with TUDCA or 4-PBA may improve stem cell function. However, whether this improvement can be translated into an in vivo clinical advantage remains to be assessed.

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“…In this study, 100 μM of capsaicin did not cause cell toxicity in brown preadipocytes but rather stimulated differentiation to brown adipocytes through the induction of ER stress. Previous studies revealed that cell differentiation was stimulated in myogenic cells, osteogenic cells and goblet cells of the intestine, when ER stress was mild 53 – 56 . We observed that treatment with tunicamycin or A23187, inducers of ER stress 42 (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…These results suggest that ER stress has a dual role in white adipogenesis; the intensity of ER stress determines cell fate during white adipogenesis. Considering that the cell differentiation is regulated by the degree of ER stress in several biological systems, as shown above 54 – 56 , appropriate levels of ER stress, which are not too strong, may be required for proper development.…”

Section: Discussionmentioning

confidence: 99%

Supra-pharmacological concentration of capsaicin stimulates brown adipogenesis through induction of endoplasmic reticulum stress

Kida

Noguchi

Murakami

et al. 2018

Sci Rep

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We previously showed that brown (pre)adipocytes express Trpv1, a capsaicin receptor, and that capsaicin stimulates differentiation of brown preadipocytes in the late stages of brown adipogenesis. The present study revealed that treatment with 100 μM capsaicin stimulates brown adipogenesis by inducing endoplasmic reticulum (ER) stress. Treatment with capsaicin (100 μM) during brown adipogenesis enhanced lipid accumulation and the expression of Ucp1, a gene selectively expressed in brown adipocytes. Capsaicin treatment also caused an increase in the cytosolic calcium concentration even when extracellular calcium was removed. I-RTX, a Trpv1 inhibitor, did not modulate the increase in cytosolic calcium concentration, lipid accumulation or Ucp1 expression. Previous studies revealed that the release of calcium from the ER induces ER stress, leading to the conversion of X-box binding protein 1 (Xbp1) pre-mRNA to spliced Xbp1 (sXbp1) as well as the up-regulation of Chop expression. Capsaicin treatment increased the expression of sXbp1 and Chop in brown preadipocytes and did not enhance lipid accumulation or Ucp1 expression in Xbp1 knockdown cells. The present results describe a novel mechanism of brown adipogenesis regulation via ER stress that is induced by a supra-pharmacological concentration of capsaicin.

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Role of the unfolded protein response in topography-induced osteogenic differentiation in rat bone marrow mesenchymal stem cells

Cited by 28 publications

References 44 publications

Nanostructured titanium regulates osseointegration via influencing macrophage polarization in the osteogenic environment

Nanostructured titanium regulates osseointegration via influencing macrophage polarization in the osteogenic environment

Bone marrow mesenchymal stem cell donors with a high body mass index display elevated endoplasmic reticulum stress and are functionally impaired

Supra-pharmacological concentration of capsaicin stimulates brown adipogenesis through induction of endoplasmic reticulum stress

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