Subchondral mesenchymal stem cells from osteoarthritic knees display high osteogenic differentiation capacity through microRNA-29a regulation of HDAC4

Lian, Wei; Wu, Ren-Wen; Lee, Mel S.; Chen, Yu‐Shan; Sun, Yi-Chih; Wu, Shing-Long; Ke, Huei-Jing; Ko, Jih‐Yang; Wang, Feng‐Sheng

doi:10.1007/s00109-017-1583-8

Cited by 18 publications

(29 citation statements)

References 51 publications

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“…Studies have reported that MSCs have a high propensity toward osteogenesis in ossification of the posterior longitudinal ligament (OPLL) patients [22]. Similarly, subchondral MSCs isolated from patients with end-stage knee OA exhibited increased proliferative and osteogenic abilities [5]. Moreover, our previous study demonstrated that BM-MSCs from AS patients displayed an abnormally enhanced osteogenic differentiation capacity in vitro [4].…”

Section: Discussionmentioning

confidence: 94%

LncRNA-OG Promotes the Osteogenic Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells Under the Regulation of hnRNPK

et al. 2018

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Bone marrow‐derived mesenchymal stem cells (BM‐MSCs) are the main source of osteoblasts in vivo and are widely used in stem cell therapy. Previously, we analyzed long noncoding RNA (lncRNA) expression profiles during BM‐MSC osteogenesis, and further investigation is needed to elucidate how lncRNAs regulate BM‐MSC osteogenesis. Herein, we used customized microarrays to determine lncRNA expression profiles in BM‐MSCs on days 0 and 10 of osteogenic differentiation. In addition, we identified a novel osteogenesis‐associated lncRNA (lncRNA‐OG) that is upregulated during this process. Functional assays showed that lncRNA‐OG significantly promotes BM‐MSC osteogenesis. Mechanistically, lncRNA‐OG interacts with heterogeneous nuclear ribonucleoprotein K (hnRNPK) protein to regulate bone morphogenetic protein signaling pathway activation. Surprisingly, hnRNPK positively regulates lncRNA‐OG transcriptional activity by promoting H3K27 acetylation of the lncRNA‐OG promoter. Therefore, our study revealed a novel lncRNA with a positive function on BM‐MSC osteogenic differentiation and proposed a new interaction between hnRNPK and lncRNA. Stem Cells 2018 Stem Cells 2019;37:270–283

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Section: Discussionmentioning

confidence: 94%

LncRNA-OG Promotes the Osteogenic Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells Under the Regulation of hnRNPK

et al. 2018

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“…In addition, spontaneous adipogenesis during osteogenic differentiation was typically much more frequent in progenitors from the iliac crest than subchondral trabecular bone from facet joint OA specimens. Reduced adipogenic potential and increased osteogenic potential have also been described in progenitors from the subchondral bone tissue of knee OA compared with bone marrow aspirates [ 22 ]. Colony formation assays under control and osteogenic conditions combined with immunohistochemical staining for Gremlin-1 would be insightful to explore the relationship between clonal phenotype and osteogenic potential and differences between distinct skeletal sites.…”

Section: Discussionmentioning

confidence: 99%

“…Gene expression arrays have shown slightly increased TGF-β1 and reduced type I collagen A2 mRNA levels in progenitor cells from lesional compared with non-lesional bone marrow tissues in hip OA [ 15 ]. In contrast, progenitor cells from explant culture of subchondral bone tissues from patients with end-stage knee OA showed lower TGF-β1 expression and higher matrix mineralization than donor-matched tibial shaft marrow aspirates [ 22 ]. High concentrations of TGF-β1 have been found in subchondral bone marrow tissues in human and experimental OA and transgenic overexpression of active TGF-β1 in subchondral bone-resident osteoblasts induced an OA-like phenotype [ 5 ].…”

Section: Discussionmentioning

confidence: 99%

Alterations of Subchondral Bone Progenitor Cells in Human Knee and Hip Osteoarthritis Lead to a Bone Sclerosis Phenotype

Bianco

Todorov

Čengić

et al. 2018

IJMS

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Subchondral bone tissue plays a key role in the initiation and progression of human and experimental osteoarthritis and has received considerable interest as a treatment target. Elevated bone turnover and remodeling leads to subchondral bone sclerosis that is characterized by an increase in bone material that is less mineralized. The aim of this study was to investigate whether perturbations in subchondral bone-resident progenitor cells might play a role in aberrant bone formation in osteoarthritis. Colony formation assays indicated similar clonogenicity of progenitor cells from non-sclerotic and sclerotic subchondral trabecular bone tissues of osteoarthritic knee and hip joints compared with controls from iliac crest bone. However, the osteogenic potential at the clonal level was approximately two-fold higher in osteoarthritis than controls. An osteogenic differentiation assay indicated an efficient induction of alkaline phosphatase activity but blunted in vitro matrix mineralization irrespective of the presence of sclerosis. Micro-computed tomography and histology demonstrated the formation of de novo calcified tissues by osteoblast-like cells in an ectopic implantation model. The expression of bone sialoprotein, a marker for osteoblast maturation and mineralization, was significantly less in sclerotic progenitor cells. Perturbation of resident progenitor cell function is associated with subchondral bone sclerosis and may be a treatment target for osteoarthritis.

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“…18 In mesenchymal stem cells, miR-29a downregulates HDAC4 and stabilizes the Wnt signaling pathway, thus enhancing osteogenic differentiation of subchondral mesenchymal stem cells (SMSCs). 19 In addition, plateletderived growth factor-BB can also phosphorylate HDAC4 in a CaMKII-dependent manner. After that, MEF2 in the nucleus is activated and promotes proliferation and migration of ROS-dependent vascular smooth muscle cells by p38/MAPK/HSP27 signaling pathway.…”

Section: Cell Proliferation and Differentiationmentioning

confidence: 99%

The posttranslational modification of HDAC4 in cell biology: Mechanisms and potential targets

Hou

Wei

Qin

et al. 2019

J of Cellular Biochemistry

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Histone deacetylase 4 (HDAC4) is a member of the HDACs family, its expression is closely related to the cell development. The cell is an independent living entity that undergoes proliferation, differentiation, senescence, apoptosis, and pathology, and each process has a strict and complex regulatory system. With deepening of its research, the expression of HDAC4 is critical in the life process. This review focuses on the posttranslational modification of HDAC4 in cell biology, providing an important target for future disease treatment.

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Subchondral mesenchymal stem cells from osteoarthritic knees display high osteogenic differentiation capacity through microRNA-29a regulation of HDAC4

Cited by 18 publications

References 51 publications

LncRNA-OG Promotes the Osteogenic Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells Under the Regulation of hnRNPK

LncRNA-OG Promotes the Osteogenic Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells Under the Regulation of hnRNPK

Alterations of Subchondral Bone Progenitor Cells in Human Knee and Hip Osteoarthritis Lead to a Bone Sclerosis Phenotype

The posttranslational modification of HDAC4 in cell biology: Mechanisms and potential targets

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