Osmolarity regulates chondrogenic differentiation potential of synovial fluid derived mesenchymal progenitor cells

Bertram, Karri L.; Krawetz, Roman

doi:10.1016/j.bbrc.2012.05.015

Cited by 33 publications

(31 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thirteen ion channels were differentially expressed between normal and OA sfMPCs (for complete microarray data, see Table S1). Based off of this data and our previous sfMPC osmolality study, 11 ion channels might play a role in the change in phenotype and function of osteoarthritic sfMPCs. Therefore, a number of ion channels present that changed in expression between normal and OA sfMPCs were studied in further detail.…”

Section: Resultssupporting

confidence: 54%

“…Our lab has shown that OA and normal sfMPCs proliferate and differentiate best in osmolality media most similar to their in vivo environment. 11 For OA cells, this is a lower osmolality (»280 mOsm) than the typical MSC culture media (»300 mOsm) used for these experiments.…”

Section: Discussionmentioning

confidence: 95%

“…12,13,14 It was recently shown in our lab that sfMPCs undergo efficient chondrogenic differentiation in vitro in a similar osmotic environment as they experienced in vivo. 11 In that study, sfMPCs were grown in vitro in hyper-and hypoosmotic conditions and while changes in chondrogenic gene expression occurred, no cell volume changes were observed. This led us to believe that ion channels may be playing a role in the behavior of sfMPCs.…”

Section: Introductionmentioning

confidence: 96%

“…The synovial fluid osmolality of OA joints is significantly lower (»280mOsm) compared to healthy joints (»400mOsm). 11 Changes in osmolality have been shown to regulate gene expression of Sox9, a central transcription factor during chondrogenesis. 12,13,14 It was recently shown in our lab that sfMPCs undergo efficient chondrogenic differentiation in vitro in a similar osmotic environment as they experienced in vivo.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Ion channel expression and function in normal and osteoarthritic human synovial fluid progenitor cells

et al. 2016

Self Cite

View full text Add to dashboard Cite

Osteoarthritis (OA) is a chronic disease affecting the cartilage of over 15% of Canadians. Synovial fluid mesenchymal progenitor cells (sfMPCs) are present in joints and are thought to contribute to healing. OA sfMPCs have a greater proliferative ability but decreased chondrogenic potential. However, little is known about the factors influencing/regulating the differences between normal and OA sfMPCs. Recently, our lab has shown that sfMPC chondrogenic differentiation in vitro is favorably biased toward a similar osmotic environment as they experience in vivo. The current study now examines the expression and functionality of a variety of ion channels in sfMPCs derived from normal individuals and early OA patients. Results indicated that there is differential ion channel regulation at the functional level and expression level in early OA sfMPCs. All ion channels were upregulated in early OA compared to normal sfMPCs with the exception of KCNMA1 at the mRNA level. At the protein level, TRPV4 was over expressed in early OA sfMPCs, while KCNJ12 and KCNMA1 were unchanged between normal and early OA sfMPCs. At the functional level, the inward rectifying potassium channel was under expressed in early OA sfMPCs, however the membrane potential was unchanged between normal and early OA sfMPCs. In the synovial environment itself, a number of differences in ion concentration between normal and early OA synovial fluid were observed. These findings suggest that normal and OA progenitor cells demonstrate functional differences in how they interact with the synovial ion environment.

show abstract

Section: Resultssupporting

confidence: 54%

Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Ion channel expression and function in normal and osteoarthritic human synovial fluid progenitor cells

et al. 2016

Self Cite

View full text Add to dashboard Cite

show abstract

“…To maintain osmotic balance, normal articular cartilage swells when exposed to hypo‐osmolality, while it shrinks under hyper‐osmolality. Different joint diseases have been shown to cause a decrease in the osmolality of the synovial fluid, particularly in osteoarthritic and rheumatoid arthritis 20, 21. In this study, osmolality was adopted as a means to induce expansion and shrinkage of the articular cartilage and its collagen fibers.…”

Section: Discussionmentioning

confidence: 99%

Non‐enzymatic cross‐linking of collagen type II fibrils is tuned via osmolality switch

Pouran

Moshtagh

Arbabi

et al. 2018

Journal Orthopaedic Research

View full text Add to dashboard Cite

An important aspect in cartilage ageing is accumulation of advanced glycation end products (AGEs) after exposure to sugars. Advanced glycation results in cross‐links formation between the collagen fibrils in articular cartilage, hampering their flexibility and making cartilage more brittle. In the current study, we investigate whether collagen cross‐linking after exposure to sugars depends on the stretching condition of the collagen fibrils. Healthy equine cartilage specimens were exposed to l‐threose sugar and placed in hypo‐, iso‐, or hyper‐osmolal conditions that expanded or shrank the tissue and changed the 3D conformation of collagen fibrils. We applied micro‐indentation tests, contrast enhanced micro‐computed tomography, biochemical measurement of pentosidine cross‐links, and cartilage surface color analysis to assess the effects of advanced glycation cross‐linking under these different conditions. Swelling of extracellular matrix due to hypo‐osmolality made cartilage less susceptible to advanced glycation, namely, the increase in effective Young's modulus was approximately 80% lower in hypo‐osmolality compared to hyper‐osmolality and pentosidine content per collagen was 47% lower. These results indicate that healthy levels of glycosaminoglycans not only keep cartilage stiffness at appropriate levels by swelling and pre‐stressed collagen fibrils, but also protect collagen fibrils from adverse effects of advanced glycation. These findings highlight the fact that collagen fibrils and therefore cartilage can be protected from further advanced glycation (“ageing”) by maintaining the joint environment at sufficiently low osmolality. Understanding of mechanochemistry of collagen fibrils provided here might evoke potential ageing prohibiting strategies against cartilage deterioration. © 2018 The Authors. Journal of Orthopaedic Research Published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. J Orthop Res 36:1929–1936, 2018.

show abstract

Cell number and chondrogenesis in human mesenchymal stem cell aggregates is affected by the sulfation level of heparin used as a cell coating

Lei

Treviño

Temenoff

2016

J Biomedical Materials Res

View full text Add to dashboard Cite

For particular cell-based therapies, it may be required to culture mesenchymal stem cell (MSC) aggregates with growth factors to promote cell proliferation and/or differentiation. Heparin, a negatively charged glycosaminoglycan (GAG) is known to play an important role in sequestration of positively charged growth factors and, when incorporated within cellular aggregates, could be used to promote local availability of growth factors. We have developed a heparin-based cell coating and we believe that the electrostatic interaction between native heparin and the positively charged growth factors will result in (1) higher cell number in response to fibroblast growth factor-2 (FGF-2) and 2) greater chondrogenic differentiation in response to transforming growth factor-β1 (TGF-β1), compared to a desulfated heparin coating. Results revealed that in the presence of FGF-2, by day 14, heparin-coated MSC aggregates increased in DNA content 8.5 ± 1.6 fold compared to day 1, which was greater than noncoated and desulfated heparin-coated aggregates. In contrast, when cultured in the presence of TGF-β1, by day 21, desulfated heparin-coated aggregates upregulated gene expression of collagen II by 86.5 ± 7.5 fold and collagen X by 37.1 ± 4.7 fold, which was higher than that recorded in the noncoated and heparin-coated aggregates. These observations indicate that this coating technology represents a versatile platform to design MSC culture systems with pairings of GAGs and growth factors that can be tailored to overcome specific challenges in scale-up and culture for MSC-based therapeutics.

show abstract

Osmolarity regulates chondrogenic differentiation potential of synovial fluid derived mesenchymal progenitor cells

Cited by 33 publications

References 29 publications

Ion channel expression and function in normal and osteoarthritic human synovial fluid progenitor cells

Ion channel expression and function in normal and osteoarthritic human synovial fluid progenitor cells

Non‐enzymatic cross‐linking of collagen type II fibrils is tuned via osmolality switch

Cell number and chondrogenesis in human mesenchymal stem cell aggregates is affected by the sulfation level of heparin used as a cell coating

Contact Info

Product

Resources

About