Effects of mechanical strain on proliferation and differentiation of bone marrow stromal cell line ST2

Koike, Mariko; Shimokawa, Hitoyata; Kanno, Zuisei; Ohya, Keiichi; Soma, Kunimichi

doi:10.1007/s00774-004-0587-y

Cited by 142 publications

(122 citation statements)

References 33 publications

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“…Hence, the response of MSCs to mechanical loading followed current models that suggest that compressive load supports chondrogenic MSC differentiation ( Table 2) (Campbell et al, 2006;Mauck et al, 2007;Pelaez et al, 2009). In contrast, osteogenic differentiation of MSCs was unaffected by cyclic compression (3D) adding weight to the notion that osteogenic differentiation requires a different mechanical stimulus, such as cyclic equibiaxial/uniaxial strain (2D) or four-point bending (Table 2) (David et al, 2007;Jagodzinski et al, 2004;Koike et al, 2005;Mauney et al, 2004). Little is known about the function of CD73 in MSCs thus far.…”

Section: Discussionmentioning

confidence: 84%

CD73/5’-ecto-nucleotidase acts as a regulatory factor in osteo-/chondrogenic differentiation of mechanically stimulated mesenchymal stromal cells

Ode

Schoon²,

Kurtz³

et al. 2013

eCM

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Bone regeneration is influenced by mesenchymal stromal cells (MSCs) and mechanical conditions. How healing outcome and mechanical stability are linked on the cellular level, however, remains elusive. Cyclic-compressive loading of MSCs affects the expression of molecules involved in angiogenesis and matrix assembly, but also reduces the expression of CD73, an ecto-5'-nucleotidase, which plays a crucial role in extracellular adenosine generation. Although, for almost 20 years, CD73 has been a major cell surface marker defining MSCs, little is known about its function in these cells. Therefore, the aim of this study was to determine the putative involvement of CD73 in MSC differentiation after cyclic-compressive loading. After cultivation in appropriate differentiation media, chondrogenic differentiation ability was significantly increased in loaded MSCs, hence following current models. Through treatment with the CD73 inhibitor adenosine 5'-(α, β-methylene) diphosphate, chondrogenic matrix deposition was further increased; in contrast, mineral matrix deposition and expression of osteogenic markers was reduced. One major signal transduction pathway, which is activated via CD73-mediated adenosine, is the adenosine receptor pathway. Thus, the adenosine receptor expression pattern was investigated. MSCs expressed the four known adenosine receptors at the mRNA level. After mechanical stimulation of MSCs, Adora2a was down-regulated. These data point towards a role of CD73 in MSC differentiation possibly via A2AR signalling, which is mutually regulated with CD73. In conclusion, the findings of this study suggest that CD73 is another regulatory factor in osteo-/ chondrogenic differentiation of MSCs and may provide a -thus far underestimated -therapeutic target to guide bone regeneration. Keywords IntroductionBone healing is a complex, however well-orchestrated, multistage regenerative process. Bone fracture coincides with disruption of blood vessels resulting in activation of the coagulation cascade and formation of the haematoma, which encloses the fracture area. Inflammatory cells, fibroblasts, and mesenchymal stromal cells (MSCs) are recruited to the site. Once MSCs have reached the bone fracture site they are confronted with a challenging milieu characterised not only by inflammatory cytokines and low oxygen tension (hypoxia) but also by constant mechanical strain (Goodship and Kenwright, 1985;Komatsu and Hadjiargyrou, 2004). This condition is likely to affect MSCs, which are known to be mechanosensitive (Wang and Thampatty, 2008). Thus, detailed knowledge about the influence of mechanical loading on MSCs is pivotal for understanding the physiological processes during bone regeneration in order to develop innovative cell therapy approaches.Recently, we and others provided evidence that mechanical strain leads to reduced expression of the cell surface marker CD73 in vitro (Kang et al., 2011;Ode et al., 2011). In our study, bone marrow (BM)-MSCs underwent cyclic-compressive loading for three days. CD73 protein a...

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Section: Discussionmentioning

confidence: 84%

CD73/5’-ecto-nucleotidase acts as a regulatory factor in osteo-/chondrogenic differentiation of mechanically stimulated mesenchymal stromal cells

Ode

Schoon²,

Kurtz³

et al. 2013

eCM

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“…Mechanical stimuli include tensile force (8,9,(11)(12)(13)(14), compressive force (7,10,(15)(16)(17), hydrostatic pressure (18), sheer stress (19,20), rotative stress (21) and others (22,23). Stimulation with tensile force using a Flexercell tension system suppresses osteoclast differentiation and fusion.…”

Section: Introductionmentioning

confidence: 99%

Release from optimal compressive force suppresses osteoclast differentiation

Ikeda

Yoshimura

Kikuiri

et al. 2016

Molecular Medicine Reports

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Abstract. Bone remodeling is an important factor in orthodontic tooth movement. During orthodontic treatment, osteoclasts are subjected to various mechanical stimuli, and this promotes or inhibits osteoclast differentiation and fusion. It has been previously reported that the release from tensile force induces osteoclast differentiation. However, little is known about how release from compressive force affects osteoclasts. The present study investigated the effects of release from compressive force on osteoclasts. The number of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated osteoclasts derived from RAW264.7 cells was counted, and gene expression associated with osteoclast differentiation and fusion in response to release from compressive force was evaluated by reverse transcription-quantitative polymerase chain reaction. Osteoclast number was increased by optimal compressive force application. On release from this force, osteoclast differentiation and fusion were suppressed. mRNA expression of NFATc1 was inhibited for 6 h subsequent to release from compressive force. mRNA expression of the other osteoclast-specific genes, TRAP, RANK, matrix metalloproteinase-9, cathepsin-K, chloride channel 7, ATPase H + transporting vacuolar proton pump member I, dendritic cell-specific transmembrane protein and osteoclast stimulatory transmembrane protein (OC-STAMP) was significantly inhibited at 3 h following release from compressive force compared with control cells. These findings suggest that release from optimal compressive force suppresses osteoclast differentiation and fusion, which may be important for developing orthodontic treatments.

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“…For example, MSCs regulated angiogenesis according to their mechanical environment. Osteogenic proliferation and differentiation appeared when MSCs were stimulated by mechanical loading (Koike et al 2005;Yoshikawa et al 1997;Kasper et al 2007;Mauney et al 2004).…”

Section: Introductionmentioning

confidence: 99%

The simulated microgravity enhances multipotential differentiation capacity of bone marrow mesenchymal stem cells

Wang

Zhang

et al. 2013

Cytotechnology

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Multi-differentiation capability is an essential characteristic of bone marrow mesenchymal stem cells (BMSCs). Method on obtaining higherquality stem cells with an improved differentiation potential has gained significant attention for the treatment of clinical diseases and developmental biology. In our study, we investigated the multipotential differentiation capacity of BMSCs under simulated microgravity (SMG) condition. F-actin staining found that cytoskeleton took on a time-dependent change under SMG condition, which caused spindle to round morphological change of the cultured cells. Quantitative PCR and Western Blotting showed the pluripotency marker OCT4 was up-regulated in the SMG condition especially after SMG of 72 h, which we observed would be the most appropriate SMG duration for enhancing pluripotency of BMSCs. After dividing BMSCs into normal gravity (NG) group and SMG group, we induced them respectively in endothelium oriented, adipogenic and neuronal induction media. Immunostaining and Western Blotting found that endothelium oriented differentiated BMSCs expressed higher VWF and CD31 in the SMG group than in the NG group. The neuron-like cells derived from BMSCs in the SMG group also expressed higher level of MAP2 and NF-H. Furthermore, the quantity of induced adipocytes increased in the SMG group compared to the NG group shown by Oil Red O staining, The expression of PPARc2 increased significantly under SMG condition. Therefore, we demonstrated that SMG could promote BMSCs to differentiate into many kinds of cells and predicted that enhanced multi-potential differentiation capacity response in BMSCs following Electronic supplementary material The online version of this article

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Effects of mechanical strain on proliferation and differentiation of bone marrow stromal cell line ST2

Cited by 142 publications

References 33 publications

CD73/5’-ecto-nucleotidase acts as a regulatory factor in osteo-/chondrogenic differentiation of mechanically stimulated mesenchymal stromal cells

CD73/5’-ecto-nucleotidase acts as a regulatory factor in osteo-/chondrogenic differentiation of mechanically stimulated mesenchymal stromal cells

Release from optimal compressive force suppresses osteoclast differentiation

The simulated microgravity enhances multipotential differentiation capacity of bone marrow mesenchymal stem cells

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