The Constitutive Expression of Type X Collagen in Mesenchymal Stem Cells from Osteoarthritis Patients Is Reproduced in a Rabbit Model of Osteoarthritis

Mwale, Fackson; Rampersad, Sonia; Richard, Hélène; Yao, Guoying; Rowas, Sora Al; Madiraju, Padma; Antoniou, John

doi:10.4061/2011/587547

Cited by 9 publications

(8 citation statements)

References 54 publications

(72 reference statements)

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“…In CM conditions, at seven days the pellets resemble the prechondrogenic mesenchyme tissue, evidenced by high expression of Col type I, confirming data from developmental studies reporting that it is highly expressed in early chondrogenesis [37][38][39][40][41][42]. The latter has then been further confirmed by the SOX9 expression [37], in both CM and CAG-supplemented pellets (Figure 4A-C).…”

Section: Discussionsupporting

confidence: 82%

Cycloastragenol as an Exogenous Enhancer of Chondrogenic Differentiation of Human Adipose-Derived Mesenchymal Stem Cells. A Morphological Study

Szychlinska

Calabrese

Ravalli

et al. 2020

Cells

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Stem cell therapy and tissue engineering represent a promising approach for cartilage regeneration. However, they present limits in terms of mechanical properties and premature de-differentiation of engineered cartilage. Cycloastragenol (CAG), a triterpenoid saponin compound and a hydrolysis product of the main ingredient in Astragalus membranaceous, has been explored for cartilage regeneration. The aim of this study was to investigate CAG’s ability to promote cell proliferation, maintain cells in their stable active phenotype, and support the production of cartilaginous extracellular matrix (ECM) in human adipose-derived mesenchymal stem cells (hAMSCs) in up to 28 days of three-dimensional (3D) chondrogenic culture. The hAMSC pellets were cultured in chondrogenic medium (CM) and in CM supplemented with CAG (CAG–CM) for 7, 14, 21, and 28 days. At each time-point, the pellets were harvested for histological (hematoxylin and eosin (H&E)), histochemical (Alcian-Blue) and immunohistochemical analysis (Type I, II, and X collagen, aggrecan, SOX9, lubricin). After excluding CAG’s cytotoxicity (MTT Assay), improved cell condensation, higher glycosaminoglycans (sGAG) content, and increased cell proliferation have been detected in CAG–CM pellets until 28 days of culture. Overall, CAG improved the chondrogenic differentiation of hAMSCs, maintaining stable the active chondrocyte phenotype in up to 28 days of 3D in vitro chondrogenic culture. It is proposed that CAG might have a beneficial impact on cartilage regeneration approaches.

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Section: Discussionsupporting

confidence: 82%

Cycloastragenol as an Exogenous Enhancer of Chondrogenic Differentiation of Human Adipose-Derived Mesenchymal Stem Cells. A Morphological Study

Szychlinska

Calabrese

Ravalli

et al. 2020

Cells

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“…In this study, anterior cruciate ligament transaction (ACLT) combined with complete medial meniscectomy was carried to induce moderate to severe OA conditions to explore the efficacy of haMPCs, although ACLT alone was investigated in other rabbit moderate OA models [ 35 , 36 , 37 ]. We found that eroded cartilage was almost completely covered by the repaired tissues, and the hyaline cartilage specific marker, collagen II expression was increased in haMPC treatment group compared with HA group.…”

Section: Discussionmentioning

confidence: 99%

Human Adipose-Derived Mesenchymal Progenitor Cells Engraft into Rabbit Articular Cartilage

Wang

Feng

et al. 2015

IJMS

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Mesenchymal stem cells (MSCs) are known to have the potential for articular cartilage regeneration, and are suggested for the treatment of osteoarthritis (OA). Here, we investigated whether intra-articular injection of xenogeneic human adipose-derived mesenchymal progenitor cells (haMPCs) promoted articular cartilage repair in rabbit OA model and engrafted into rabbit articular cartilage. The haMPCs were cultured in vitro, and phenotypes and differentiation characteristics of cells were evaluated. OA was induced surgically by anterior cruciate ligament transection (ACLT) and medical meniscectomy of knee joints. At six weeks following surgery, hyaluronic acid (HA) or haMPCs was injected into the knee joints, the contralateral knee served as normal control. All animals were sacrificed at the 16th week post-surgery. Assessments were carried out by macroscopic examination, hematoxylin/eosin (HE) and Safranin-O/Fast green stainings and immunohistochemistry. The data showed that haMPC treatment promoted cartilage repair. Signals of human mitochondrial can be directly detected in haMPC treated cartilage. The haMPCs expressed human leukocyte antigen I (HLA-I) but not HLA-II-DR in vivo. These results suggest that intra-articular injection of haMPCs promotes regeneration of articular cartilage in rabbit OA model, and support the notion that MPCs are transplantable between HLA-incompatible individuals.

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“…There are contradictory data regarding hypertrophic chondrocyte in OA. Some publications have indicated that terminal differentiation of chondrocytes into hypertrophy is associated with OA [ 6 , 43 , 44 ]. Therefore hypertrophy chondrocyte is considered as one of the hallmarks in OA.…”

Section: Discussionmentioning

confidence: 99%

Type X collagen levels are elevated in serum from human osteoarthritis patients and associated with biomarkers of cartilage degradation and inflammation

Siebuhr

Brandt-Hansen

et al. 2014

BMC Musculoskelet Disord

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BackgroundOsteoarthritis (OA) is the most common degenerative joint disease, of which the pathogenesis is inadequately understood. Hypertrophy-like changes have been observed as part of the progression of OA. The aim of the study was to develop and characterize a novel biomarker of chondrocytes hypertrophy and investigate how this marker was associated with cartilage degradation and inflammation in patients with various degrees of OA.MethodsA competitive ELISA, C-Col10, applying a well-characterized monoclonal antibody was developed as a biomarker of chondrocyte hypertrophy through measurement of type X collagen (ColX). The levels of C-Col10, C2M (matrix metalloproteinase-derived fragments of type II collagen) and hsCRP (high sensitive C-reactive protein) were quantified by ELISAs in serum of 271 OA patients stratified by Kellgren-Lawrence (KL) score 0–4. Associations between serum levels of the three biomarkers (log transformed) were analyzed by Pearson’s correlation and differences in C-Col10 levels between patients with high and low levels of inflammation measured by hsCRP were analyzed by ANOVA.ResultsWe developed a C-Col10 assay measuring the C-terminus of ColX. We found significantly higher levels of ColX in patients with KL score 2 compared to patients with no radiographic evidence of OA (KL0) (p = 0.04). Levels of ColX were significantly elevated in OA patients with above normal hsCRP levels (p < 0.0001), as well as significantly correlated with levels of C2M (r = 0.55, p < 0.0001), which suggested that chondrocyte hypertrophy was associated with inflammation and cartilage degradation. There was no correlation between C2M and hsCRP. Age and BMI adjustment didn’t change the results. Immuno-staining revealed that ColX was predominately located around the hypertrophic chondrocytes and the clustered chondrocytes indicating that C-Col10 measures may be linked to cartilage hypertrophic changes.ConclusionsWe developed a novel assay, C-Col10, for measurement of chondrocyte hypertrophy and found its levels significantly elevated in OA patients with KL score of 2, and also in OA patients with above normal hsCRP levels. Concentration of C-Col10 strongly correlated with levels of C2M, a marker of cartilage destruction. The data suggest that chondrocyte hypertrophy and subsequent collagen X fragmentation seem to be increased in a subset of patients with inflammatory OA.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2474-15-309) contains supplementary material, which is available to authorized users.

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The Constitutive Expression of Type X Collagen in Mesenchymal Stem Cells from Osteoarthritis Patients Is Reproduced in a Rabbit Model of Osteoarthritis

Cited by 9 publications

References 54 publications

Cycloastragenol as an Exogenous Enhancer of Chondrogenic Differentiation of Human Adipose-Derived Mesenchymal Stem Cells. A Morphological Study

Cycloastragenol as an Exogenous Enhancer of Chondrogenic Differentiation of Human Adipose-Derived Mesenchymal Stem Cells. A Morphological Study

Human Adipose-Derived Mesenchymal Progenitor Cells Engraft into Rabbit Articular Cartilage

Type X collagen levels are elevated in serum from human osteoarthritis patients and associated with biomarkers of cartilage degradation and inflammation

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