scholarly journals Evaluation of the Impact of Different Pain Medication and Proton Pump Inhibitors on the Osteogenic Differentiation Potential of hMSCs Using 99mTc-HDP Labelling

Life ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 339
Author(s):  
Tobias Grossner ◽  
Uwe Haberkorn ◽  
Tobias Gotterbarm

First-line analgetic medication used in the field of musculoskeletal degenerative diseases, like Nonsteroidal anti-inflammatory drugs (NSAIDs), reduces pain and prostaglandin synthesis, whereby peptic ulcers are a severe adverse effect. Therefore, proton pump inhibitors (PPI) are frequently used as a concomitant medication to reduce this risk. However, the impact of NSAIDs or metamizole, in combination with PPIs, on bone metabolism is still unclear. Therefore, human mesenchymal stem cells (hMSCs) were cultured in monolayer cultures in 10 different groups for 21 days. New bone formation was induced as follows: Group 1 negative control group, group 2 osteogenic differentiation media (OSM), group 3 OSM with pantoprazole (PAN), group 4 OSM with ibuprofen (IBU), group 5 OSM with diclofenac (DIC), group 6 OSM with metamizole (MET), group 7 OSM with ibuprofen and pantoprazole (IBU + PAN), group 8 OSM with diclofenac and pantoprazole (DIC + PAN), group 9 OSM with metamizole and pantoprazole (MET + PAN) and group 10 OSM with diclofenac, metamizole and pantoprazole (DIC + MET + PAN). Hydroxyapatite content was evaluated using high-sensitive radioactive 99mTc-HDP labeling. Within this study, no evidence was found that the common analgetic medication, using NSAIDs alone or in combination with pantoprazole and/or metamizole, has any negative impact on the osteogenic differentiation of mesenchymal stem cells in vitro. To the contrary, the statistical results indicate that pantoprazole alone (group 3 (PAN) (p = 0.016)) or diclofenac alone (group 5 (DIC) (p = 0.008)) enhances the deposition of minerals by hMSCS in vitro. There is an ongoing discussion between clinicians in the field of orthopaedics and traumatology as to whether post-surgical (pain) medication has a negative impact on bone healing. This is the first hMSC in vitro study that investigates the effects of pain medication in combination with PPIs on bone metabolism. Our in vitro data indicates that the assumed negative impact on bone metabolism is subsidiary. These findings substantiate the thesis that, in clinical medicine, the patient can receive every pain medication needed, whether or not in combination with PPIs, without any negative effects for the osteo-regenerative potential.

2018 ◽  
Vol 18 (1) ◽  
pp. 69-86
Author(s):  
Joanna Romanek ◽  
Jolanta Opiela ◽  
Zdzisław Smorąg

AbstractThe aim of the present study was to examine the influence of two varied high hydrostatic pressure (HHP) values on the apoptosis (assessing caspase-8, survivin, CAD, Bax, BclxL and BclxS) and functional activity (using cocultures with bovine embryos) of porcine mesenchymal stem cells (pBMSCs). pBMSCs were isolated from porcine bone marrow and cultured in vitro. Before cryopreservation and storage in liquid nitrogen, pBMSCs were subjected to HHP values of 40 MPa and 60 MPa for 1 h at 24°C. After thawing, the cells were analysed for caspase-8 activity and protein expression of survivin, CAD, Bax, BclxL and BclxS. To indirectly test the influence of HHP on the functional activity of pBMSCs, in vitro maturated bovine oocytes were fertilized in vitro, and the obtained embryos were cultured under 4 different conditions: 1. monoculture in SOF medium; 2. coculture with pBMSCs in SOF medium; 3. coculture with pBMSCs subjected to 40 MPa HHP in SOF medium and 4. coculture with pBMSCs subjected to 60 MPa HHP in SOF medium. The quality of the developed blastocysts was analysed by TUNEL assay. HHP did not induce apoptosis in pBMSCs, as no significant difference was noted in the expression of any of the analysed apoptosis- related proteins between pBMSCs subjected to HHP (40 MPa or 60 MPa) and control. The highest number of obtained blastocysts was observed when the embryos were cultured in SOF. A highly significant difference (P<0.005) was noted between embryos cultured in SOF and embryos cultured in the presence of pBMSCs subjected to 60 MPa HHP or untreated pBMSCs. A significant difference (P<0.05) was noted between embryos cultured in SOF and embryos cultured in the presence of pBMSCs subjected to 40 MPa HHP. In conclusion, HHP does not induce apoptosis in pBMSCs. The obtained results of the blastocysts cocultured in vitro with pBMSCs (HHP-treated and untreated cells) imply that coculture with pBMSCs has a negative impact on the developmental rates of blastocysts.


2012 ◽  
Vol 1498 ◽  
pp. 39-45
Author(s):  
Courtney E. LeBlon ◽  
Caitlin R. Fodor ◽  
Tony Zhang ◽  
Xiaohui Zhang ◽  
Sabrina S. Jedlicka

ABSTRACTHuman mesenchymal stem cells (hMSCs) were routinely cultured on tissue-culture polystyrene (TCPS) to investigate the in vitro aging and cell stiffening. hMSCs were also cultured on thermoplastic polyurethane (TPU), which is a biocompatible polymer with an elastic modulus of approximately 12.9MPa, to investigate the impact of substrate elastic modulus on cell stiffening and differentiation potential. Cells were passaged over several generations on each material. At each passage, cells were subjected to osteogenic and myogenic differentiation. Local cell elastic modulus was measured at every passage using atomic force microscopy (AFM) indentation. Gene and protein expression was examined using qRT-PCR and immunofluorescent staining, respectively, for osteogenic and myogenic markers. Results show that the success of myogenic differentiation is highly reliant on the elastic modulus of the undifferentiated cells. The success of osteogenic differentiations is most likely somewhat dependent on the cell elastic modulus, as differentiations were more successful in earlier passages, when cells were softer.


2016 ◽  
Vol 367 (2) ◽  
pp. 257-267 ◽  
Author(s):  
Hua-ji Jiang ◽  
Xing-gui Tian ◽  
Shou-bin Huang ◽  
Guo-rong Chen ◽  
Min-jun Huang ◽  
...  

RSC Advances ◽  
2019 ◽  
Vol 9 (16) ◽  
pp. 9117-9125
Author(s):  
Ting Ma ◽  
Xi-Yuan Ge ◽  
Ke-Yi Hao ◽  
Xi Jiang ◽  
Yan Zheng ◽  
...  

Titanium discs with simple 3,4-dihydroxy-l-phenylalanine coating enhanced BM-MSC adhesion, spreading, proliferation and differentiation, and upregulated expression of genes involved in focal adhesion in vitro.


Author(s):  
Lizhi Han ◽  
Song Gong ◽  
Ruoyu Wang ◽  
Shaokai Liu ◽  
Bo Wang ◽  
...  

Steroid-induced osteonecrosis of femoral head (SONFH) is a common and serious complication caused by long-term and/or excessive use of glucocorticoids (GCs). The decreased activity and abnormal differentiation of bone marrow mesenchymal stem cells (BMSCs) are considered to be one of the major reasons for the onset and progression of this disease. Periostin (POSTN) is a matricellular protein which plays an important role in regulating osteoblast function and bone formation. Sclerostin (SOST) is a secreted antagonist of Wnt signaling that is mainly expressed in osteocytes to inhibit bone formation. However, the exact role of POSTN and SOST in SONFH has not been reported yet. Therefore, we detected the differential expression of POSTN and SOST in BMSCs of SONFH Group patients, and Control Group was patients with traumatic ONFH (TONFH) and developmental dysplasia of the hip (DDH). Furthermore, we used lentiviral transfection to knockdown POSTN expression in BMSCs of patients with SONFH to study the effect of POSTN knockdown on the SOST expression and osteogenic differentiation of BMSCs. The results indicated that the endogenous expression of POSTN and SOST in BMSCs of SONFH Group was upregulated, compared with Control Group. POSTN was upregulated gradually while SOST was downregulated gradually at days 0, 3, and 7 of osteogenic differentiation of BMSCs in Control Group. Contrarily, POSTN was gradually downregulated while SOST was gradually upregulated during osteogenic differentiation of BMSCs in SONFH Group. This could be due to increased expression of SOST in BMSCs, which was caused by excessive GCs. In turn, the increased expression of POSTN in BMSCs may play a role in antagonizing the continuous rising of SOST during the osteogenic differentiation of BMSCs in patients with SONFH. POSTN knockdown significantly attenuated osteo-specific gene expression, alkaline phosphatase activity, and calcium nodule formation in vitro; thus inhibiting the osteogenic differentiation of BMSCs in patients with SONFH. Besides, POSTN knockdown upregulated SOST expression, increased GSK-3β activity, and downregulated β-catenin. These findings suggest that POSTN have an essential role in regulating the expression of SOST and osteogenic differentiation of BMSCs in patients with SONFH, and POSTN knockdown suppresses osteogenic differentiation by upregulating SOST and partially inactivating Wnt/β-catenin signaling pathway. Therefore, targeting POSTN and SOST may serve as a promising therapeutic target for the prevention and treatment of SONFH.


2019 ◽  
Vol 9 (3) ◽  
pp. 377-388 ◽  
Author(s):  
Elisa Mazzoni ◽  
Antonio D'Agostino ◽  
Maria Rosa Iaquinta ◽  
Ilaria Bononi ◽  
Lorenzo Trevisiol ◽  
...  

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