Multilineage Differentiation of Dental Pulp Stem Cells from Green Fluorescent Protein Transgenic Mice

Grottkau, Brian E.; Purudappa, Prabhudev Prasad; Lin, Yunfeng

doi:10.4248/ijos10015

Cited by 36 publications

(27 citation statements)

References 21 publications

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“…6,30 In vivo data show that increased bone resorption occurs at an early stage in the development of OA and that blocking bone-resorbing cytokines prevents cartilage damage; 2,31 these data infer the bone factors may play an important role in cartilage behaviour. We found that secreted factors from osteoclasts modulated the gelatinase activity in chondrocytes.…”

Section: Discussionmentioning

confidence: 99%

The effects of interleukin-1β in modulating osteoclast-conditioned medium’s influence on gelatinases in chondrocytes through mitogen-activated protein kinases

Xie

Cai

et al. 2015

Int J Oral Sci

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Osteoarthritis is recognised to be an interactive pathological process involving the cartilage, subchondral bone and synovium. The signals from the synovium play an important role in cartilage metabolism, but little is known regarding the influence of the signalling from bone. Additionally, the collagenases and stromelysin-1 are involved in cartilage catabolism through mitogen-activated protein kinase (MAPK) signalling, but the role of the gelatinases has not been elucidated. Here, we studied the influence of osteoclastic signals on chondrocytes by characterising the expression of interleukin-1β (IL-1β)-induced gelatinases through MAPK signalling. We found that osteoclast-conditioned media attenuated the gelatinase activity in chondrocytes. However, IL-1β induced increased levels of gelatinase activity in the conditioned media group relative to the mono-cultured chondrocyte group. More specifically, IL-1β restored high levels of gelatinase activity in c-Jun N-terminal kinase inhibitor-pretreated chondrocytes in the conditioned media group and led to lower levels of gelatinase activity in extracellular signal-regulated kinase or p38 inhibitor-pretreated chondrocytes. Gene expression generally correlated with protein expression. Taken together, these results show for the first time that signals from osteoclasts can influence gelatinase activity in chondrocytes. Furthermore, these data show that IL-1β restores gelatinase activity through MAPK inhibitors; this information can help to increase the understanding of the gelatinase modulation in articular cartilage.

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Section: Discussionmentioning

confidence: 99%

The effects of interleukin-1β in modulating osteoclast-conditioned medium’s influence on gelatinases in chondrocytes through mitogen-activated protein kinases

Xie

Cai

et al. 2015

Int J Oral Sci

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“…There have been no prior studies on the uptake of exosomes by DPSCs or on the effects of pulp-specific exosomes on the odontogenic differentiation of DPSCs and HMSCs. DPSCs are mesenchymal stem cells derived from the neural crest and possess multi-lineage differentiation potential [50–53]. On the other hand HMSCs are marrow derived stromal cells also capable of multi-lineage differentiation.…”

Section: Discussionmentioning

confidence: 99%

Exosomes as biomimetic tools for stem cell differentiation: Applications in dental pulp tissue regeneration

et al. 2016

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Achieving and maintaining safe and reliable lineage specific differentiation of stem cells is important for clinical translation of tissue engineering strategies. In an effort to circumvent the multitude of problems arising from the usage of growth factors and growth factor delivery systems, we have explored the use of exosomes as biomimetic tools to induce stem cell differentiation. Working on the hypothesis that cell-type specific exosomes can trigger lineage-specific differentiation of stem cells, we have evaluated the potential of exosomes derived from dental pulp cells cultured on under growth and odontogenic differentiation conditions to induce odontogenic differentiation of naïve human dental pulp stem cells (DPSCs) and human bone marrow derived stromal cells (HMSCs) in vitro and in vivo. Results indicate that the exosomes can bind to matrix proteins such as type I collagen and fibronectin enabling them to be tethered to biomaterials. The exosomes are endocytosed by both DPSCs and HMSCs in a dose-dependent and saturable manner via the caveolar endocytic mechanism and trigger the P38 mitogen activated protein kinase (MAPK) pathway. In addition, the exosomes also trigger the increased expression of genes required for odontogenic differentiation. When tested in vivo in a tooth root slice model with DPSCs, the exosomes triggered regeneration of dental pulp-like tissue. However, our results indicate that exosomes isolated under odontogenic conditions are better inducers of stem cell differentiation and tissue regeneration. Overall, our results highlight the potential exosomes as biomimetic tools to induce lineage specific differentiation of stem cells. Our results also show the importance of considering the source and state of exosome donor cells before a choice is made for therapeutic applications.

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“…To elucidate what kind of stem cell markers are expressed in the LRCs in this study using FACS in the future would guide us to new perspectives in stem cell biology, because it is more difficult and even impossible to identify stem cells in the tissue. Furthermore, green fluorescent protein transgenic mice could be available for the analysis of the relationship between dense LRCs and DPSCs, because DPSCs expressing endogenous GFP maintain their ability to differentiate (Grottkau et al 2010).…”

Section: Mapping Of Lrcs In the Growing Toothmentioning

confidence: 99%

The relationship between cell proliferation and differentiation and mapping of putative dental pulp stem/progenitor cells during mouse molar development by chasing BrdU-labeling

et al. 2012

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Human dental pulp contains adult stem cells. Our recent study demonstrated the localization of putative dental pulp stem/progenitor cells in the rat developing molar by chasing 5-bromo-2'-deoxyuridine (BrdU)-labeling. However, there are no available data on the localization of putative dental pulp stem/progenitor cells in the mouse molar. This study focuses on the mapping of putative dental pulp stem/progenitor cells in addition to the relationship between cell proliferation and differentiation in the developing molar using BrdU-labeling. Numerous proliferating cells appeared in the tooth germ and the most active cell proliferation in the mesenchymal cells occurred in the prenatal stages, especially on embryonic Day 15 (E15). Cell proliferation in the pulp tissue dramatically decreased in number by postnatal Day 3 (P3) when nestin-positive odontoblasts were arranged in the cusped areas and disappeared after postnatal Week 1 (P1W). Root dental papilla included numerous proliferating cells during P5 to P2W. Three to four intraperitoneal injections of BrdU were given to pregnant ICR mice and revealed slow-cycling long-term label-retaining cells (LRCs) in the mature tissues of postnatal animals. Numerous dense LRCs postnatally decreased in number and reached a plateau after P1W when they mainly resided in the center of the dental pulp, associating with blood vessels. Furthermore, numerous dense LRCs co-expressed mesenchymal stem cell markers such as STRO-1 and CD146. Thus, dense LRCs in mature pulp tissues were believed to be dental pulp stem/progenitor cells harboring in the perivascular niche surrounding the endothelium.

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Multilineage Differentiation of Dental Pulp Stem Cells from Green Fluorescent Protein Transgenic Mice

Abstract: Aim The aim of this study was to confirm the multilineage differentiation ability of dental pulp stem cells (DPSCs)

Cited by 36 publications

References 21 publications

The effects of interleukin-1β in modulating osteoclast-conditioned medium’s influence on gelatinases in chondrocytes through mitogen-activated protein kinases

The effects of interleukin-1β in modulating osteoclast-conditioned medium’s influence on gelatinases in chondrocytes through mitogen-activated protein kinases

Exosomes as biomimetic tools for stem cell differentiation: Applications in dental pulp tissue regeneration

The relationship between cell proliferation and differentiation and mapping of putative dental pulp stem/progenitor cells during mouse molar development by chasing BrdU-labeling

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