Effect of aged bone marrow microenvironment on mesenchymal stem cell migration

Abstract

Mesenchymal stem cells (MSCs) are known to have many notable features, especially their multiple differentiation ability and immunoregulatory capacity. MSCs are important stem cells in the bone marrow (BM), and their characteristics are affected by the BM microenvironment. However, effects of the BM microenvironment on the properties of MSCs are not well understood. In this study, we found that BM from aged mice decreased MSC colony formation. Flow cytometry data showed that the proportion of B220 + cells in BM from aged mice was significantly lower than that in BM from young mice, while the proportion of CD11b + , CD3 + , Gr-1 + , or F4/80 + cells are on the contrary. CD11b + , B220 + , and Ter119 + cells from aged mice were not the subsets that decreased MSC colony formation. We further demonstrated that both BM from aged mice and young mice exhibited similar effects on the proliferation of murine MSC cell line C3H10T1/2. However, when cocultured with BM from aged mice, C3H10T1/2 showed slower migration ability. In addition, we found that phosphorylation of JNK (c-Jun N-terminal kinases) in C3H10T1/2 cocultured with BM from aged mice was lower than that in C3H10T1/2 cocultured with BM from young mice. Collectively, our data revealed that BM from aged mice could decrease the migration of MSCs from their niche through regulating the JNK pathway.

A bone-resorption surface-targeting nanoparticle to deliver anti-miR214 for osteoporosis therapy

“…synthesis of asp 8 -PU D8-PEG-COOH (1 mg) was dissolved in deionized water and reacted with 1 mg 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and 1 mg N-hydroxysuccinimide at 4°C for 10 minutes. PU micelles were subsequently added to D8 peptide solutions and the mixture reacted overnight at 4°C.…”

“…Asp 8 -PU nanoparticles were ~80 nm, with narrow size distribution and average ζ-potential 13.6 mV ( Figure 1C). The nucleic acid-binding capacity of Asp 8 -PU nanomicelles was assessed by gel electrophoresis, and data indicated that nucleic acid mobility was retarded by Asp 8 -PU nanomicelles at Asp 8 -PU:nucleic acid (w:w) weight ratios greater than 10:1 ( Figure 1D). After incubation with serum for 6 hours, electrophoretic assays indicated that a band representing free nucleic acid was degraded, but the Asp 8 -PU-nucleic acid band was still visible after incubation with serum for 24 hours ( Figure 1E).…”

“…7 Therefore, to correct the imbalance in bone remodeling, inhibiting the formation and activity of osteoclasts should be a preferred method. 8 To enhance bone-formation ability, drugs are delivered to the bone-formation area or osteoblasts. [9][10][11] To inhibit the function of osteoclasts efficiently, the delivery system should preferentially deliver drug to the bone-resorption area or osteoclasts.…”

“…Bone-resorption surfaces are characterized by highly crystallized hydroxyapatite. 30 The peptide Asp 8 , which is highly negatively charged, has been reported as a bone-resorption area-targeting tool. 31 In this study, Asp 8 was used as the targeting part of the delivery system.…”

“…30 The peptide Asp 8 , which is highly negatively charged, has been reported as a bone-resorption area-targeting tool. 31 In this study, Asp 8 was used as the targeting part of the delivery system. Mounting evidence has shown that miRNA drugs are good candidates for OP treatment through regulation of the activity of functional cells.…”