Evidence map›Paper›PMID 27255741›Full record

ArticleArthritis research & therapy2016

Notochordal cell conditioned medium (NCCM) regenerates end-stage human osteoarthritic articular chondrocytes and promotes a healthy phenotype.

Sebastian Müller, Lina Acevedo, Xiaomei Wang, M Zia Karim, Ajay Matta, Arne Mehrkens, Stefan Schaeren, Sandra Feliciano, Marcel Jakob, Ivan Martin and 2 more

Abstract read
In one paragraph

Article in Arthritis research & therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed.

  1. Article
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  8. Experimental Therapeutics for the Treatment of Osteoarthritis.Journal of experimental pharmacology · 2021
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Sebastian MüllerDepartment of Orthopaedics and Traumatology, University Hospital Basel, Spitalstrasse 21, 4031 Basel, Switzerland.
Lina AcevedoDepartment of Biomedicine, University Hospital Basel, University of Basel, Hebelstrasse 20, 4031 Basel, Switzerland.
Xiaomei WangKrembil Research Institute, Toronto Western Hospital, Divisions of Neurological and Orthopaedic Surgery, University of Toronto, 60 Leonard Street, KDT5-407, Toronto, ON, M5K 1K2, Canada.
M Zia KarimKrembil Research Institute, Toronto Western Hospital, Divisions of Neurological and Orthopaedic Surgery, University of Toronto, 60 Leonard Street, KDT5-407, Toronto, ON, M5K 1K2, Canada.
Ajay MattaKrembil Research Institute, Toronto Western Hospital, Divisions of Neurological and Orthopaedic Surgery, University of Toronto, 60 Leonard Street, KDT5-407, Toronto, ON, M5K 1K2, Canada.
Arne MehrkensDepartment of Biomedicine, University Hospital Basel, University of Basel, Hebelstrasse 20, 4031 Basel, Switzerland.
Stefan SchaerenDepartment of Biomedicine, University Hospital Basel, University of Basel, Hebelstrasse 20, 4031 Basel, Switzerland.
Sandra FelicianoDepartment of Biomedicine, University Hospital Basel, University of Basel, Hebelstrasse 20, 4031 Basel, Switzerland.
Marcel JakobDepartment of Orthopaedics and Traumatology, University Hospital Basel, Spitalstrasse 21, 4031 Basel, Switzerland.
Ivan MartinDepartment of Biomedicine, University Hospital Basel, University of Basel, Hebelstrasse 20, 4031 Basel, Switzerland.
Andrea BarberoDepartment of Biomedicine, University Hospital Basel, University of Basel, Hebelstrasse 20, 4031 Basel, Switzerland.
W Mark ErwinKrembil Research Institute, Toronto Western Hospital, Divisions of Neurological and Orthopaedic Surgery, University of Toronto, 60 Leonard Street, KDT5-407, Toronto, ON, M5K 1K2, Canada. mark.erwin@utoronto.ca.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundNotochordal cell conditioned medium (NCCM) derived from non-chondrodystrophic dogs has pro-anabolic and anti-catabolic effects upon nucleus pulposus (NP) cells. Here, for the first time, we assessed the ability of NCCM to influence the production of extracellular matrix and inflammatory proteins by healthy and osteoarthritic human chondrocytes within engineered cartilage tissues. We hypothesized that, similar to its action on NP cells, NCCM exerts metabolic and anti-catabolic effects on human articular chondrocytes and has the potential to significantly counteract inflammatory mediators.

methodsChondrocytes from nine non-osteoarthritic patients and from six osteoarthritic (OA) donors at the time of total knee arthroplasty were chondro-differentiated in pellets for 2 weeks. Non-OA pellets were exposed for 72 hours to IL-1β/TNF-α and then cultured up to 14 days in 2 % FBS-supplemented NCCM or 2 % FBS-supplemented medium (control (ctr)). OA pellets were cultured in NCCM or ctr medium without pro-inflammatory treatment. Tissues after each culture phase were analyzed biochemically (GAG/DNA), (immuno-) histologically (collagen I, II and GAG) and by Western blotting. Supernatants were analyzed by ELISA.

resultsResponse to NCCM was age and disease dependent with healthy chondrocyte pellets (from donors >55 years of age) recovering their glycosaminoglycan (GAG) contents to baseline levels only with NCCM. OA pellets treated with NCCM significantly increased GAG content (1.8-fold) and levels of hyaluronic acid link protein (HAPLN), fibromodulin and SOX-9. The catabolic proteins (matrix metalloproteinase (MMP)-3 and MMP-13) and pro-inflammatory enzyme levels (cyclooxygenase-2 (COX-2)) were markedly reduced and there was significantly reduced secretion of pro-inflammatory chemokines (IL-6 and IL-8).

conclusionsNCCM restores cartilage matrix production of end-stage human OA chondrocytes towards a healthy phenotype and suppresses the production of inflammatory mediators. Harnessing the necessary and sufficient factors within NCCM that confers chondroprotection and regenerative effects could lead to a minimally invasive agent for treatment of degenerative and inflammatory joint diseases.

Indexed as

NotochordOsteoarthritisAdolescentAdultAgedAged, 80 and overAnimalsBlotting, WesternCartilage, ArticularCell DifferentiationChondrocytesCulture Media, ConditionedDogsEnzyme-Linked Immunosorbent AssayFemaleHumansCulture Media, ConditionedCartilageNotochordal cell conditioned mediumOA chondrocytesOA treatmentRegenerative medicine

Identifiers

PMID27255741
PMCPMC4890286

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.