Inhibition of STAT5A promotes osteogenesis by DLX5 regulation

Lee, Kyoung Mi; Park, Kwang Hwan; Hwang, Ji Suk; Lee, Moses; Yoon, Dong Suk; Ryu, Hyun Aae; Jung, Ho Sun; Park, Ki Won; Kim, Jihyun; Sw, Park; Kim, Sung Hwan; Chun, Yong-Min; Choi, Woo Jin; Lee, Jin Woo

doi:10.1038/s41419-018-1184-7

Cited by 26 publications

(20 citation statements)

References 48 publications

(51 reference statements)

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“…Unsurprisingly, it could also influence the molecular markers of osteoblastic lineage. RUNX2, SP7 and DLX5 are mandatory transcriptional factors regulating the osteogenic process 39 , 40 . The overall transcription levels of SP7 and DLX5 were significantly declined following knockdown of OMD during osteogenesis.…”

Section: Discussionmentioning

confidence: 99%

Osteomodulin positively regulates osteogenesis through interaction with BMP2

et al. 2021

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Osteomodulin (OMD), a member of the small leucine-rich proteoglycan family, distributes in mineralized tissues and is positively regulated by bone morphogenetic protein 2 (BMP2). However, the exact function of OMD during mineralization and its association with BMP2 remain poorly understood. Herein, the expression pattern of OMD during osteogenesis was investigated in human dental pulp stem cells. Silencing OMD gene significantly suppressed the alkaline phosphatase activity, mineralized nodule formation and osteogenesis-associated gene transcription. Besides, OMD could enhance BMP2-induced expression of SP7 and RUNX2 with concentration dependence in vitro. Rat mandibular bone defect model revealed that scaffolds injected with the combination of OMD and suboptimal BMP2 exhibited more mature and abundant mineralized bone than that treated with OMD or suboptimal BMP2 alone. Mechanistically, OMD could bind to BMP2 via its terminal leucine-rich repeats and formed complexes with BMP2 and its membrane receptors, thus promoting BMP/SMAD signal transduction. In addition, OMD was a putative target gene of SMAD4, which plays a pivotal role in this pathway. Collectively, these data elucidate that OMD may act as a positive coordinator in osteogenesis through BMP2/SMADs signaling.

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Section: Discussionmentioning

confidence: 99%

Osteomodulin positively regulates osteogenesis through interaction with BMP2

et al. 2021

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“…Therefore, both Stat5a and Stat5b show extensive similarities regarding their sequence with isoform-specific functions. Deletion of Stat5a leads to increased bone mineral density, trabecular and cortical bone mass and prevents age-related bone loss in mice [66]. Lee et al investigated the role of STAT5a in human bone marrow-derived mesenchymal stromal cells.…”

Section: Guiding Bone Development By Combining Jaks and Statsmentioning

confidence: 99%

JAK/STAT Activation: A General Mechanism for Bone Development, Homeostasis, and Regeneration

Damerau

Gaber

Ohrndorf

et al. 2020

IJMS

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The Janus kinase (JAK) signal transducer and activator of transcription (STAT) signaling pathway serves as an important downstream mediator for a variety of cytokines, hormones, and growth factors. Emerging evidence suggests JAK/STAT signaling pathway plays an important role in bone development, metabolism, and healing. In this light, pro-inflammatory cytokines are now clearly implicated in these processes as they can perturb normal bone remodeling through their action on osteoclasts and osteoblasts at both intra- and extra-articular skeletal sites. Here, we summarize the role of JAK/STAT pathway on development, homeostasis, and regeneration based on skeletal phenotype of individual JAK and STAT gene knockout models and selective inhibition of components of the JAK/STAT signaling including influences of JAK inhibition in osteoclasts, osteoblasts, and osteocytes.

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“…BMPs and BMP receptors control the differentiation of mesenchymal stem cells [38,39,51,52] in very complex cooperation with several other pathways and transcription factors [53] such as Wnt, Notch, fibroblast growth factor (FGF), or sonic hedgehog (Shh) and players of these signaling pathways [54]. These pathways can be also altered by several factors that may affect the differentiation of mesenchymal stem cells [55][56][57]. The evaluation of our data also revealed, that after 1 week of incubation, the induced BMP-7 expression negatively affects the ALP activity of the DPSC-BMP-7 cell line both in CM+ and OM+ and this effect is prolonged to 3 weeks in CM+.…”

Section: Discussionmentioning

confidence: 99%

Effect of Inducible BMP-7 Expression on the Osteogenic Differentiation of Human Dental Pulp Stem Cells

Tóth

Tőzsér

Hegedűs

2021

IJMS

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BMP-7 has shown inductive potential for in vitro osteogenic differentiation of mesenchymal stem cells, which are an ideal resource for regenerative medicine. Externally applied, recombinant BMP-7 was able to induce the osteogenic differentiation of DPSCs but based on our previous results with BMP-2, we aimed to study the effect of the tetracyclin-inducible BMP-7 expression on these cells. DPSC, mock, and DPSC-BMP-7 cell lines were cultured in the presence or absence of doxycycline, then alkaline phosphatase (ALP) activity, mineralization, and mRNA levels of different osteogenic marker genes were measured. In the DPSC-BMP-7 cell line, the level of BMP-7 mRNA significantly increased in the media supplemented with doxycycline, however, the expression of Runx2 and noggin genes was upregulated only after 21 days of incubation in the osteogenic medium with doxycycline. Moreover, while the examination of ALP activity showed reduced activity in the control medium containing doxycycline, the accumulation of minerals remained unchanged in the cultures. We have found that the induced BMP-7 expression failed to induce osteogenic differentiation of DPSCs. We propose three different mechanisms that may worth investigating for the engineering of expression systems that can be used for the induction of differentiation of mesenchymal stem cells.

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Inhibition of STAT5A promotes osteogenesis by DLX5 regulation

Cited by 26 publications

References 48 publications

Osteomodulin positively regulates osteogenesis through interaction with BMP2

Osteomodulin positively regulates osteogenesis through interaction with BMP2

JAK/STAT Activation: A General Mechanism for Bone Development, Homeostasis, and Regeneration

Effect of Inducible BMP-7 Expression on the Osteogenic Differentiation of Human Dental Pulp Stem Cells

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