Enhanced Osteogenic Differentiation of Human Bone Marrow Mesenchymal Stem Cells in Ossification of the Posterior Longitudinal Ligament Through Activation of the BMP2-Smad1/5/8 Pathway.

Abstract:

:Ossification of the posterior longitudinal ligament (OPLL) is characterized by ectopic OPLL. To date, the specific molecular pathogenesis of OPLL has not been clearly elucidated. In this study, bone marrow-derived mesenchymal stem cells obtained from healthy donors (HD-MSCs) and patients with OPLL (OPLL-MSCs) were cultured in osteogenic differentiation medium for 21 days. The osteogenic differentiation capacity was determined by alizarin red S (ARS) and alkaline phosphatase (ALP) assays. Gene expression levels of osteoblastic markers were measured by quantitative reverse transcription-polymerase chain reaction. Protein levels of related genes and the activation of related signaling pathways were measured by western blotting. LDN193189 was used to inhibit the Smad1/5/8 pathway, and small interfering RNA was used to regulate BMP2 expression. Our results showed that the OPLL-MSCs had stronger ARS staining and ALP activity and higher expression of RUNX2, Osterix, and OCN than the HD-MSCs. During osteogenic differentiation, the Smad1/5/8 pathway was overactivated in the OPLL-MSCs, and LDN193189 inhibition reversed the enhanced osteogenic ability of these cells. Besides, BMP2 was upregulated in the OPLL-MSCs. After BMP2 knockdown, the abnormal osteogenic differentiation of OPLL-MSCs was rescued. Thus, abnormal activation of the BMP2-Smad1/5/8 pathway induces enhanced osteogenic differentiation of OPLL-MSCs compared with HD-MSCs. These findings reveal a mechanism of pathological osteogenesis in OPLL and provide a new perspective on inhibiting pathological osteogenesis by regulating BMP2.

journal_name

Stem Cells Dev

authors

Cai Z,Wu B,Ye G,Liu W,Chen K,Wang P,Xie Z,Li J,Zheng G,Yu W,Su Z,Lin J,Wu Y,Shen H

doi

10.1089/scd.2020.0117

subject

Has Abstract

pub_date

2020-12-01 00:00:00

pages

1567-1576

issue

24

eissn

1547-3287

issn

1557-8534

journal_volume

29

pub_type

杂志文章
  • Role of low voltage activated calcium channels in neuritogenesis and active migration of embryonic neural progenitor cells.

    abstract::The central role of calcium influx and electrical activity in embryonic development raises important questions about the role and regulation of voltage-dependent calcium influx. Using cultured neural progenitor cell (NPC) preparations, we recorded barium currents through voltage-activated channels using the whole-cell...

    journal_title:Stem cells and development

    pub_type: 杂志文章

    doi:10.1089/scd.2012.0234

    authors: Louhivuori LM,Louhivuori V,Wigren HK,Hakala E,Jansson LC,Nordström T,Castrén ML,Akerman KE

    更新日期:2013-04-15 00:00:00

  • Mesenchymal stem cell and chondrocyte fates in a multishear microdevice are regulated by Yes-associated protein.

    abstract::Mechanical cues exert considerable influence on the fates of stem cells and terminally differentiated chondrocytes. The elucidation of the interactions between cell fate and mechanical cues in nuclear mechanotransduction will provide new clues to modulate tissue homeostasis and regeneration. In this study, we used an ...

    journal_title:Stem cells and development

    pub_type: 杂志文章

    doi:10.1089/scd.2012.0685

    authors: Zhong W,Tian K,Zheng X,Li L,Zhang W,Wang S,Qin J

    更新日期:2013-07-15 00:00:00

  • Long-Term Culture of Porcine Induced Pluripotent Stem-Like Cells Under Feeder-Free Conditions in the Presence of Histone Deacetylase Inhibitors.

    abstract::The reprogramming of somatic cells to induced pluripotent stem cells (iPSCs) is a complex process that involves significant epigenetic alterations in the reprogrammed cells. Epigenetic modifiers such as histone deacetylase (HDAC) inhibitors have been shown to increase the efficiency of derivation of iPSCs in humans an...

    journal_title:Stem cells and development

    pub_type: 杂志文章

    doi:10.1089/scd.2015.0317

    authors: Petkov S,Glage S,Nowak-Imialek M,Niemann H

    更新日期:2016-03-01 00:00:00

  • Attitudes to Stem Cell Therapy Among Ischemic Stroke Survivors in the Lund Stroke Recovery Study.

    abstract::Preclinical studies suggest that stem cell therapy (SCT) may improve poststroke recovery, and clinical trials investigating safety are ongoing. However, knowledge about patients' attitudes to SCT in stroke is limited. We evaluated the knowledge and attitudes to this therapeutic approach as well as possible factors inf...

    journal_title:Stem cells and development

    pub_type: 杂志文章

    doi:10.1089/scd.2016.0343

    authors: Aked J,Delavaran H,Lindvall O,Norrving B,Kokaia Z,Lindgren A

    更新日期:2017-04-15 00:00:00

  • The NOTCH Ligand JAG1 Regulates GDNF Expression in Sertoli Cells.

    abstract::In the seminiferous epithelium of the testis, Sertoli cells are key niche cells directing proliferation and differentiation of spermatogonial stem cells (SSCs) into spermatozoa. Sertoli cells produce glial cell line-derived neurotrophic factor (GDNF), which is essential for SSC self-renewal and progenitor expansion. W...

    journal_title:Stem cells and development

    pub_type: 杂志文章

    doi:10.1089/scd.2016.0318

    authors: Garcia TX,Parekh P,Gandhi P,Sinha K,Hofmann MC

    更新日期:2017-04-15 00:00:00

  • Identification of Ccr4-not complex components as regulators of transition from partial to genuine induced pluripotent stem cells.

    abstract::Somatic cells can be reprogrammed to induced pluripotent stem cells (iPSCs) by defined factors. However, substantial cell numbers subjected to iPSC induction stray from the main reprogramming route and are immortalized as partial iPSCs. These partial iPSCs can become genuine iPSCs by exposure to the ground state condi...

    journal_title:Stem cells and development

    pub_type: 杂志文章

    doi:10.1089/scd.2013.0326

    authors: Kamon M,Katano M,Hiraki-Kamon K,Hishida T,Nakachi Y,Mizuno Y,Okazaki Y,Suzuki A,Hirasaki M,Ueda A,Nishimoto M,Kato H,Okuda A

    更新日期:2014-09-15 00:00:00

  • Splenectomy influences homing of transplanted stem cells in bone marrow-ablated mice.

    abstract::Cell mobilization, a process that influences circulation, margination, and finally, homing play key roles in the regeneration processes mediated by stem cells. Recent studies as well as prior studies from our group indicate an important role of the spleen in hematopoietic reconstitution, but to date the role of the sp...

    journal_title:Stem cells and development

    pub_type: 杂志文章

    doi:10.1089/scd.2011.0068

    authors: Filip S,Mokrý J,Vávrová J,Cížková D,Sinkorová Z,Mičuda S,Bláha M,English D

    更新日期:2012-03-20 00:00:00

  • Role of nanotechnology in epigenetic reprogramming.

    abstract::With the recent advances in regenerative medicine, nanotechnology has created a niche for itself as a promising avenue in this field. Innumerable studies have been carried out by researchers using virus-based methodologies for the purpose of epigenetic reprogramming. Although this method is ostensibly safe, nonetheles...

    journal_title:Stem cells and development

    pub_type: 杂志文章,评审

    doi:10.1089/scd.2014.0309

    authors: Kadengodlu PA,Rai VR

    更新日期:2015-03-01 00:00:00

  • Identification of Multipotent Stem Cells in Human Brain Tissue Following Stroke.

    abstract::Perivascular regions of the brain harbor multipotent stem cells. We previously demonstrated that brain pericytes near blood vessels also develop multipotency following experimental ischemia in mice and these ischemia-induced multipotent stem cells (iSCs) can contribute to neurogenesis. However, it is essential to unde...

    journal_title:Stem cells and development

    pub_type: 杂志文章

    doi:10.1089/scd.2016.0334

    authors: Tatebayashi K,Tanaka Y,Nakano-Doi A,Sakuma R,Kamachi S,Shirakawa M,Uchida K,Kageyama H,Takagi T,Yoshimura S,Matsuyama T,Nakagomi T

    更新日期:2017-06-01 00:00:00

  • In Vivo Neural Tissue Engineering: Cylindrical Biocompatible Hydrogels That Create New Neural Tracts in the Adult Mammalian Brain.

    abstract::Individuals with neurodegenerative disorders or brain injury have few treatment options and it has been proposed that endogenous adult neural stem cells can be harnessed to repopulate dysfunctional nonneurogenic regions of the brain. We have accomplished this through the development of rationally designed hydrogel imp...

    journal_title:Stem cells and development

    pub_type: 杂志文章

    doi:10.1089/scd.2016.0069

    authors: Clark AR,Carter AB,Hager LE,Price EM

    更新日期:2016-08-01 00:00:00

  • Glycosylated Cell Surface Markers for the Isolation of Human Cardiac Progenitors.

    abstract::The aim of stem cell therapy after cardiac injury is to replace damaged cardiac tissue. Human cardiac progenitor cells (CPCs) represent an interesting cell population for clinical strategies to treat cardiac disease and human CPC-specific antibodies would aid in the clinical implementation of cardiac progenitor-based ...

    journal_title:Stem cells and development

    pub_type: 杂志文章

    doi:10.1089/scd.2017.0048

    authors: Moerkamp AT,Leung HW,Bax NAM,Holst S,Lodder K,Berends T,Dingenouts CKE,Choo A,Smits AM,Goumans MJ

    更新日期:2017-11-01 00:00:00

  • Alteration Analysis of Bone Marrow Mesenchymal Stromal Cells from De Novo Acute Myeloid Leukemia Patients at Diagnosis.

    abstract::Bone marrow (BM)-derived mesenchymal stromal cells (MSCs) frequently display alterations in several hematologic disorders, such as acute lymphoid leukemia, acute myeloid leukemia (AML), and myelodysplastic syndromes. In acute leukemias, it is not clear whether MSC alterations contribute to the development of the malig...

    journal_title:Stem cells and development

    pub_type: 杂志文章

    doi:10.1089/scd.2016.0295

    authors: Desbourdes L,Javary J,Charbonnier T,Ishac N,Bourgeais J,Iltis A,Chomel JC,Turhan A,Guilloton F,Tarte K,Demattei MV,Ducrocq E,Rouleux-Bonnin F,Gyan E,Hérault O,Domenech J

    更新日期:2017-05-15 00:00:00

  • Effects of aging on osteogenic response and heterotopic ossification following burn injury in mice.

    abstract::Heterotopic ossification (HO) is a common and debilitating complication of burns, traumatic brain injuries, and musculoskeletal trauma and surgery. Although the exact mechanism of ectopic bone formation is unknown, mesenchymal stem cells (MSCs) capable of osteogenic differentiation are known to play an essential role....

    journal_title:Stem cells and development

    pub_type: 杂志文章

    doi:10.1089/scd.2014.0291

    authors: Peterson JR,Eboda ON,Brownley RC,Cilwa KE,Pratt LE,De La Rosa S,Agarwal S,Buchman SR,Cederna PS,Morris MD,Wang SC,Levi B

    更新日期:2015-01-15 00:00:00

  • Human Cardiac-Mesenchymal Stem Cell-Like Cells, a Novel Cell Population with Therapeutic Potential.

    abstract::Cardiac stem/progenitors are being used in the clinic to treat patients with a range of cardiac pathologies. However, improvements in heart function following treatment have been reported to be variable, with some showing no response. This discrepancy in response remains unresolved. Mesenchymal stem cells (MSCs) have ...

    journal_title:Stem cells and development

    pub_type: 杂志文章

    doi:10.1089/scd.2018.0170

    authors: Oldershaw R,Owens WA,Sutherland R,Linney M,Liddle R,Magana L,Lash GE,Gill JH,Richardson G,Meeson A

    更新日期:2019-05-01 00:00:00

  • Ionizing Radiation Impacts on Cardiac Differentiation of Mouse Embryonic Stem Cells.

    abstract::Little is known about the effects of ionizing radiation on the earliest stages of embryonic development although it is well recognized that ionizing radiation is a natural part of our environment and further exposure may occur due to medical applications. The current study addresses this issue using D3 mouse embryonic...

    journal_title:Stem cells and development

    pub_type: 杂志文章

    doi:10.1089/scd.2015.0260

    authors: Helm A,Arrizabalaga O,Pignalosa D,Schroeder IS,Durante M,Ritter S

    更新日期:2016-01-15 00:00:00

  • Human liver progenitor cell lines are readily established from non-tumorous tissue adjacent to hepatocellular carcinoma.

    abstract::Non-tumorous liver tissue removed during surgery to resect hepatocellular carcinoma (HCC) is potentially a useful source of material from which cells, particularly liver progenitor/stem cells (LPCs), can be isolated to establish cell lines. The purpose of this study was to evaluate the applicability of the "plate-and-...

    journal_title:Stem cells and development

    pub_type: 杂志文章

    doi:10.1089/scd.2009.0304

    authors: Zhang A,London R,Schulz FM,Giguère-Simmonds PW,Delriviere L,Chandraratana H,Hardy K,Zheng S,Olynyk JK,Yeoh G

    更新日期:2010-08-01 00:00:00

  • Expression of Reg family proteins in embryonic stem cells and its modulation by Wnt/beta-catenin signaling.

    abstract::Regenerating islet (Reg) proteins are involved in the proliferation and differentiation of diverse cell types. However, whether embryonic stem cells (ESCs) express Reg genes and their corresponding proteins remains unknown. In this study, we probed the expression of Reg family members by mouse ESCs (mESCs). Mouse Reg1...

    journal_title:Stem cells and development

    pub_type: 杂志文章

    doi:10.1089/scd.2009.0398

    authors: Jing D,Kehoe DE,Tzanakakis ES

    更新日期:2010-09-01 00:00:00

  • Human embryonic and induced pluripotent stem cells express TRAIL receptors and can be sensitized to TRAIL-induced apoptosis.

    abstract::Death ligands and their tumor necrosis factor receptor (TNFR) family receptors are the best-characterized and most efficient inducers of apoptotic signaling in somatic cells. In this study, we analyzed whether these prototypic activators of apoptosis are also expressed and able to be activated in human pluripotent ste...

    journal_title:Stem cells and development

    pub_type: 杂志文章

    doi:10.1089/scd.2013.0057

    authors: Vinarsky V,Krivanek J,Rankel L,Nahacka Z,Barta T,Jaros J,Andera L,Hampl A

    更新日期:2013-11-15 00:00:00

  • Ddx46 is required for multi-lineage differentiation of hematopoietic stem cells in zebrafish.

    abstract::Balanced and precisely controlled processes between self-renewal and differentiation of hematopoietic stem cells (HSCs) into all blood lineages are critical for vertebrate definitive hematopoiesis. However, the molecular mechanisms underlying the maintenance and differentiation of HSCs have not been fully elucidated. ...

    journal_title:Stem cells and development

    pub_type: 杂志文章

    doi:10.1089/scd.2012.0623

    authors: Hirabayashi R,Hozumi S,Higashijima S,Kikuchi Y

    更新日期:2013-09-15 00:00:00

  • Cultivation in human serum reduces adipose tissue-derived mesenchymal stromal cell adhesion to laminin and endothelium and reduces capillary entrapment.

    abstract::The increasing use of mesenchymal stromal cells (MSC) in clinical cellular therapy requires a safe and controlled production process compliant with Good Manufacturing Practice guidelines. Pooled blood group AB human serum (HS) has been used to replace fetal bovine serum (FBS), critically rated by the regulatory agenci...

    journal_title:Stem cells and development

    pub_type: 杂志文章

    doi:10.1089/scd.2012.0051

    authors: Dreher L,Elvers-Hornung S,Brinkmann I,Huck V,Henschler R,Gloe T,Klüter H,Bieback K

    更新日期:2013-03-01 00:00:00

  • Nonhuman primate models in translational regenerative medicine.

    abstract::Humans and nonhuman primates (NHPs) are similar in size, behavior, physiology, biochemistry, structure and function of organs, and complexity of the immune system. Research on NHPs generates complementary data that bridge translational research from small animal models to humans. NHP models of human disease offer uniq...

    journal_title:Stem cells and development

    pub_type: 杂志文章

    doi:10.1089/scd.2014.0374

    authors: Daadi MM,Barberi T,Shi Q,Lanford RE

    更新日期:2014-12-01 00:00:00

  • Depsipeptide (FK228) preferentially induces apoptosis in BCR/ABL-expressing cell lines and cells from patients with chronic myelogenous leukemia in blast crisis.

    abstract::Resistance to imatinib can occur in patients with chronic myelogenous leukemia (CML). In this study, we report mechanisms of action of histone deacetylase (HDAC) inhibitor, depsipeptide (FK228) in BCR/ABL-expressing cell lines and its effectiveness in imatinib-resistant cells from patients with blast crisis of CML. FK...

    journal_title:Stem cells and development

    pub_type: 杂志文章

    doi:10.1089/scd.2007.9994

    authors: Okabe S,Tauchi T,Nakajima A,Sashida G,Gotoh A,Broxmeyer HE,Ohyashiki JH,Ohyashiki K

    更新日期:2007-06-01 00:00:00

  • Immunogenicity of adult mesenchymal stem cells: lessons from the fetal allograft.

    abstract::Herein we review recent data that support host tolerance of allogeneic adult mesenchymal stem cells (MSC). Evidence is emerging that donor MSC deploy a very powerful array of mechanisms that allow escape from host allogeneic responses. These mechanisms include limited expression of alloantigen by the stem cell and cel...

    journal_title:Stem cells and development

    pub_type: 杂志文章,评审

    doi:10.1089/scd.2005.14.252

    authors: Barry FP,Murphy JM,English K,Mahon BP

    更新日期:2005-06-01 00:00:00

  • Teratogenic potential in cultures optimized for oligodendrocyte development from mouse embryonic stem cells.

    abstract::We describe a rapid and efficient 5-step program of defined factors for the genesis of brain myelin-forming oligodendrocytes (OLs) from embryonic stem cells (ESCs). The OLs emerge on the same time frame in vitro as seen in vivo. Factors promoting neural induction (retinoids, noggin) are required, while exogenous Sonic...

    journal_title:Stem cells and development

    pub_type: 杂志文章

    doi:10.1089/scd.2009.0520

    authors: Sadowski D,Kiel ME,Apicella M,Arriola AG,Chen CP,McKinnon RD

    更新日期:2010-09-01 00:00:00

  • In vitro direct osteogenesis of murine embryonic stem cells without embryoid body formation.

    abstract::Embryonic stem cells (ESCs) posses the ability to self-renew and differentiate into a multitude of lineages, including the osteogenic lineage in vitro. Currently, most approaches have focused on embryonic body (EB)-mediated osteogenic differentiation, which relies on formation of all three germ layers resulting in lim...

    journal_title:Stem cells and development

    pub_type: 杂志文章

    doi:10.1089/scd.2007.0228

    authors: Hwang YS,Polak JM,Mantalaris A

    更新日期:2008-10-01 00:00:00

  • Ochratoxin A inhibits adipogenesis through the extracellular signal-related kinases-peroxisome proliferator-activated receptor-γ pathway in human adipose tissue-derived mesenchymal stem cells.

    abstract::Ochratoxin A (OTA) is a ubiquitous fungal metabolite with nephrotoxic, carcinogenic, and apoptotic potential. Although the toxic effects of OTA in various cell types are well characterized, it is not known whether OTA has an effect on stem cell differentiation. In this study, we demonstrate that OTA inhibits adipogene...

    journal_title:Stem cells and development

    pub_type: 杂志文章

    doi:10.1089/scd.2010.0071

    authors: Lim S,Jang HJ,Kim JK,Kim JM,Park EH,Yang JH,Kim YH,Yea K,Ryu SH,Suh PG

    更新日期:2011-03-01 00:00:00

  • Downregulation of the Canonical WNT Signaling Pathway by TGFβ1 Inhibits Photoreceptor Differentiation of Adult Human Müller Glia with Stem Cell Characteristics.

    abstract::Müller glia are responsible for the retina regeneration observed in zebrafish. Although the human retina harbors Müller glia with stem cell characteristics, there is no evidence that they regenerate the retina after disease or injury. Transforming growth factor-β (TGFβ) and Wnt signaling regulate retinal neurogenesis ...

    journal_title:Stem cells and development

    pub_type: 杂志文章

    doi:10.1089/scd.2015.0262

    authors: Angbohang A,Wu N,Charalambous T,Eastlake K,Lei Y,Kim YS,Sun XH,Limb GA

    更新日期:2016-01-01 00:00:00

  • The in vivo developmental potential of porcine skin-derived progenitors and neural stem cells.

    abstract::Multipotent skin-derived progenitors (SKPs) can be traced back to embryonic neural crest cells and are able to differentiate into both neural and mesodermal progeny in vitro. Neural stem cells (NSCs) are capable of self-renewing and can contribute to neuron and glia in the nervous system. Recently, we derived porcine ...

    journal_title:Stem cells and development

    pub_type: 杂志文章

    doi:10.1089/scd.2012.0067

    authors: Zhao MT,Yang X,Lee K,Mao J,Teson JM,Whitworth KM,Samuel MS,Spate LD,Murphy CN,Prather RS

    更新日期:2012-09-20 00:00:00

  • Generation and characterization of an immortalized human mesenchymal stromal cell line.

    abstract::Human mesenchymal stromal cells (hMSCs) show great potential for clinical and experimental use due to their capacity to self-renew and differentiate into multiple mesenchymal lineages. However, disadvantages of primary cultures of hMSCs are the limited in vitro lifespan, and the variable properties of cells from diffe...

    journal_title:Stem cells and development

    pub_type: 杂志文章

    doi:10.1089/scd.2013.0599

    authors: Skårn M,Noordhuis P,Wang MY,Veuger M,Kresse SH,Egeland EV,Micci F,Namløs HM,Håkelien AM,Olafsrud SM,Lorenz S,Haraldsen G,Kvalheim G,Meza-Zepeda LA,Myklebost O

    更新日期:2014-10-01 00:00:00

  • In vitro multilineage differentiation and self-renewal of single pancreatic colony-forming cells from adult C57BL/6 mice.

    abstract::In a previous study we established colony assays suitable for studying murine adult (2-4 months) pancreatic progenitor cells plated in semisolid media containing methylcellulose and extracellular matrix proteins. Using these assays, we found robust in vitro progenitor cell activities (multilineage differentiation and ...

    journal_title:Stem cells and development

    pub_type: 杂志文章

    doi:10.1089/scd.2013.0466

    authors: Jin L,Feng T,Zerda R,Chen CC,Riggs AD,Ku HT

    更新日期:2014-04-15 00:00:00