Bone morphogenetic protein-2 enhances the osteogenic differentiation capacity of mesenchymal stromal cells derived from human bone marrow and umbilical cord

Marupanthorn, Kulisara; Tantrawatpan, Chairat; Kheolamai, Pakpoom; Tantikanlayaporn, Duangrat; Manochantr, Sirikul

doi:10.3892/ijmm.2017.2872

Cited by 64 publications

(60 citation statements)

References 40 publications

(49 reference statements)

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“…MSCs isolated from human umbilical cord (hUCMSCs), which is routinely discarded as clinical waste, has the similar capacities of cell proliferation, differentiation and immunosuppression to human bone marrow MSCs (Ennis, Gotherstrom, Le Blanc, & Davies, 2008;Ullah, Subbarao, & Rho, 2015). hUCMSC has been demonstrated to be a promising alternative source of MSC (Hou et al, 2009;Klontzas, Kenanidis, Heliotis, Tsiridis, & Mantalaris, 2015;Marupanthorn, Tantrawatpan, Kheolamai, Tantikanlayaporn, & Manochantr, 2017). However, the role and mechanism of the hUCMSCsecreted ECM constructs (hUCMSC-ECM) on bone formation remain unknown in vivo.…”

Section: Introductionmentioning

confidence: 99%

IGFBP3 deposited in the human umbilical cord mesenchymal stem cell‐secreted extracellular matrix promotes bone formation

Deng

Luo

Hou

et al. 2018

Journal Cellular Physiology

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The extracellular matrix (ECM) contains rich biological cues for cell recruitment, proliferationm, and even differentiation. The osteoinductive potential of scaffolds could be enhanced through human bone marrow mesenchymal stem cell (hBMSC) directly depositing ECM on surface of scaffolds. However, the role and mechanism of human umbilical cord mesenchymal stem cells (hUCMSC)‐secreted ECM in bone formation remain unknown. We tested the osteoinductive properties of a hUCMSC‐secreted ECM construct (hUCMSC‐ECM) in a large femur defect of a severe combined immunodeficiency (SCID) mouse model. The hUCMSC‐ECM improved the colonization of endogenous MSCs and bone regeneration, similar to the hUCMSC‐seeded scaffold and superior to the scaffold substrate. Besides, the hUCMSC‐ECM enhanced the promigratory molecular expressions of the homing cells, including CCR2 and TβRI. Furthermore, the hUCMSC‐ECM increased the number of migrated MSCs by nearly 3.3 ± 0.1‐fold, relative to the scaffold substrate. As the most abundant cytokine deposited in the hUCMSC‐ECM, insulin‐like growth factor binding protein 3 (IGFBP3) promoted hBMSC migration in the TβRI/II‐ and CCR2‐dependent mechanisms. The hUCMSC‐ECM integrating shRNA‐mediated silencing of Igfbp3 that down‐regulated IGFBP3 expression by approximately 60%, reduced the number of migrated hBMSCs by 47%. In vivo, the hUCMSC‐ECM recruited 10‐fold more endogenous MSCs to initiate bone formation compared to the scaffold substrate. The knock‐down of Igfbp3 in the hUCMSC‐ECM inhibited nearly 60% of MSC homing and bone regeneration capacity. This research demonstrates that IGFBP3 is an important MSC homing molecule and the therapeutic potential of hUCMSC‐ECM in bone regeneration is enhanced by improving MSC homing in an IGFBP3‐dependent mechanism.

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Section: Introductionmentioning

confidence: 99%

IGFBP3 deposited in the human umbilical cord mesenchymal stem cell‐secreted extracellular matrix promotes bone formation

Deng

Luo

Hou

et al. 2018

Journal Cellular Physiology

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“…Osteoblast‐derived osteocalcin, osteonectin, and FGF23 have opposing effects for bone matrix formation . BM stromal cells secrete BMP2, which enhances the osteoblast differentiation from MSCs and osteoblast functions . Accumulated adipocytic cells in BM lead to generation of DPP4, which impairs bone regeneration .…”

Section: Resultsmentioning

confidence: 99%

Suboptimal Level of Bone‐Forming Cells in Advanced Cirrhosis are Associated with Hepatic Osteodystrophy

Bihari

Lal

Thakur

et al. 2018

Hepatology Communications

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Bone loss is common in advanced cirrhosis, although the precise mechanisms underlying bone loss in cirrhosis are unknown. We studied the profile and functionality of bone‐forming cells and bone‐building proteins in bone marrow (BM) of individuals with cirrhosis (n = 61) and individuals without cirrhosis as normal controls (n = 50). We also performed dual energy X‐ray absorptiometry for clinical correlation. BM mesenchymal cells (MSCs) were analyzed for colony‐forming units‐fibroblasts and their osteogenic (fibronectin‐1 [FN1], insulin‐like growth factor binding protein 3 [IGFBP3], collagen type 1 alpha 1 chain [COL1A1], runt‐related transcription factor 2 [RUNX2], and alkaline phosphatase, liver [ALPL]) and adipogenic ( adiponectin, C1Q, and collagen domain containing [ADIPOQ], peroxisome proliferator‐activated receptor gamma [PPARγ], and fatty acid binding protein 4 [FABP4]) potentials. Colony‐forming units‐fibroblasts were lower in patients with cirrhosis (P = 0.002) than in controls. Cirrhotic BM‐MSCs showed >2‐fold decrease in osteogenic markers. Compared to controls, patients with cirrhosis showed fewer osteocytes (P = 0.05), osteoblasts, chondroblasts, osteocalcin‐positive (osteocalcin+) area, clusters of differentiation (CD)169+ macrophages (P < 0.001, each), and nestin+ MSCs (P = 0.001); this was more apparent in Child‐Turcotte‐Pugh (CTP) class C than A (P < 0.001). Multivariate logistic regression showed low nestin+ MSCs (P = 0.004) as a predictor of bone loss. Bone‐resolving osteoclasts were comparable among CTP groups, but >2‐fold decreased anti‐osteoclastic and increased pro‐osteoclastic factors were noted in patients with CTP C compared to CTP A. Bone‐building proteins (osteocalcin [P = 0.008], osteonectin [P < 0.001], and bone morphogenic protein 2 [P = 0.001]) were decreased while anti‐bone repair factors (fibroblast growth factor 23 [P = 0.015] and dipeptidyl peptidase 4 [P < 0.001]) were increased in BM and peripheral blood; this was more apparent in advanced cirrhosis. The dual energy X‐ray absorptiometry scan T score significantly correlated with the population of osteoblasts, osteocytes, MSCs, and CD169+ macrophages. Conclusion: Osteoprogenitor cells are substantially reduced in patients with cirrhosis and more so in advanced disease. Additionally, increased anti‐bone repair proteins enhance the ineffective bone repair and development of osteoporosis in cirrhosis. Hepatology Communications 2018;0:0‐0)

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“…Osteoblasts are mainly derived from bone marrow mesenchymal stem cells, the differentiation process of which is dependent on the regulation of a number of transcription factors and cytokines (20). Bone marrow mesenchymal stem cells are pluripotent stem cells that can differentiate into osteoblasts, chondrocytes and adipocytes (21). A previous study revealed that when the cells have high expressions of Runx2 and OSX, mesenchymal stem cells are differentiated into osteoblasts (21).…”

Section: Discussionmentioning

confidence: 99%

“…Bone marrow mesenchymal stem cells are pluripotent stem cells that can differentiate into osteoblasts, chondrocytes and adipocytes (21). A previous study revealed that when the cells have high expressions of Runx2 and OSX, mesenchymal stem cells are differentiated into osteoblasts (21). However, when these cells highly express sex-determining region Y-box 9, mesenchymal stem cells are differentiated into chondrocytes, and when they have a high expression of PPAR, they differentiate into chondrocytes (22).…”

Section: Discussionmentioning

confidence: 99%

Epigallocatechin‑3‑gallate protects against secondary osteoporosis in a mouse model via the Wnt/β‑catenin signaling pathway

Luo

et al. 2018

Mol Med Report

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Epigallocatechin‑3‑gallate (EGCG) is a polyphenolic compound extracted and isolated from green tea, which has a variety of important biological activities in vitro and in vivo, including anti‑tumor, anti‑oxidation, anti‑inflammation and lowering blood pressure. The aim of the present study was to investigate the protective effect of EGCG against secondary osteoporosis in a mouse model via the Wnt/β‑catenin signaling pathway. Reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and western blotting were used to analyze runt‑related transcription factor 2 and osterix mRNA expression, and the protein expression of cyclin D1, Wnt and β‑catenin, and suppressed peroxisome proliferator‑activated receptor γ protein expression. The protective effect of EGCG against secondary osteoporosis was examined and its potential mechanism was analyzed. Treatment with EGCG significantly decreased serum calcium, urinary calcium, body weight and body fat, and increased leptin levels in mice with secondary osteoporosis. In addition, EGCG treatment significantly inhibited the structure score of articular cartilage and cancellous bone in proximal tibia metaphysis in mice with secondary osteoporosis. Treatment also significantly decreased alkaline phosphatase activity, runt‑related transcription factor 2 and osterix mRNA expression. EGCG also significantly induced the protein expression of cyclin D1, Wnt and β‑catenin, and suppressed peroxisome proliferator‑activated receptor γ protein expression in mice with secondary osteoporosis. Taken together, these results suggest that EGCG may be a possible new drug in clinical settings.

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Bone morphogenetic protein-2 enhances the osteogenic differentiation capacity of mesenchymal stromal cells derived from human bone marrow and umbilical cord

Cited by 64 publications

References 40 publications

IGFBP3 deposited in the human umbilical cord mesenchymal stem cell‐secreted extracellular matrix promotes bone formation

IGFBP3 deposited in the human umbilical cord mesenchymal stem cell‐secreted extracellular matrix promotes bone formation

Suboptimal Level of Bone‐Forming Cells in Advanced Cirrhosis are Associated with Hepatic Osteodystrophy

Epigallocatechin‑3‑gallate protects against secondary osteoporosis in a mouse model via the Wnt/β‑catenin signaling pathway

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