Maturity-dependent cartilage cell plasticity and sensitivity to external perturbation

Walsh, Shannon K.; Schneider, Stephanie; Amundson, Laura A; Neu, Corey P.; Henak, Corinne R.

doi:10.1016/j.jmbbm.2020.103732

Cited by 7 publications

(10 citation statements)

References 51 publications

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“…As a unique marker or marker set is lacking, MSC or chondrocyte markers are mostly used for identification (Table 1 ). Classical MSC markers CD105 21 – 23 , CD166 24 , CD146 25 , VCAM 26 , or combinations including these markers 27 , 28 have been used by others. In essence, this results in the identification of an MSC-like population in articular cartilage.…”

Section: Resultsmentioning

confidence: 99%

“…The highest frequency in the superficial layer. Inhibition of NF-κB pathway increased ACPCs in OA progression and lowered OARSI scores Zhang et al 21 Rat Hip Unknown CD105 + /integrin-α5β1 + co-expression CD105 + /integrin-α5β1 + cells are activated by partial-thickness cartilage defects Cai et al 45 Rat Knee ACLT-induced OA CD44E + /CD90 + co-expression Recovery of CD44E + /CD90 + cells in cartilage after ACLT and treatment with HA and magnoflorine Walsh et al 23 Porcine Knee Unknown Mechanical loading of immature, adolescent, and mature cartilage followed by surface marker expression, gene expression, and histology Increased expression of CD105 and CD29 in immature cartilage; decreased expression of ACAN, Col-X and SOX9 in immature cartilage, increased expression of Col-I, Col-II in immature cartilage Dowthwaite et al 16 Bovine Articular cartilage (surface, middle, and deep zone) Unknown Expression of integrin-α5, integrin-β1, fibronectin, and Notch-1 All markers are mainly expressed in the superficial zone Jang et al 35 Bovine Stifle (tibial plateau) Unknown Calcein-AM/Ethidium homodimer staining of cells migrated into fibrin in partial- and full-thickness defects, treated with low-intensity pulsed ultrasound More cells migrated in low-intensity pulsed treated defects. FAK activation increased in treated samples Seol et al 32 Bovine and human Stifle (bovine) and talus (human) Healthy Morphology Increased number of elongated cells in impacted cartilage explants of both species Ustunel et al 29 Human Knee (intercondylar notch) Healthy Expression of Notch-1, Notch-2, Notch-3, Notch-4, Delta, Jagged-1, and Jagged-2 Notch-1 and Delta were abundantly expressed in the superficial zone Grogan et al 26 Human Knee …”

Section: Resultsmentioning

confidence: 99%

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The clinical potential of articular cartilage-derived progenitor cells: a systematic review

et al. 2022

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Over the past two decades, evidence has emerged for the existence of a distinct population of endogenous progenitor cells in adult articular cartilage, predominantly referred to as articular cartilage-derived progenitor cells (ACPCs). This progenitor population can be isolated from articular cartilage of a broad range of species, including human, equine, and bovine cartilage. In vitro, ACPCs possess mesenchymal stromal cell (MSC)-like characteristics, such as colony forming potential, extensive proliferation, and multilineage potential. Contrary to bone marrow-derived MSCs, ACPCs exhibit no signs of hypertrophic differentiation and therefore hold potential for cartilage repair. As no unique cell marker or marker set has been established to specifically identify ACPCs, isolation and characterization protocols vary greatly. This systematic review summarizes the state-of-the-art research on this promising cell type for use in cartilage repair therapies. It provides an overview of the available literature on endogenous progenitor cells in adult articular cartilage and specifically compares identification of these cell populations in healthy and osteoarthritic (OA) cartilage, isolation procedures, in vitro characterization, and advantages over other cell types used for cartilage repair. The methods for the systematic review were prospectively registered in PROSPERO (CRD42020184775).

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

The clinical potential of articular cartilage-derived progenitor cells: a systematic review

et al. 2022

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“…3B ), suggesting that age-associated factors limit this important developmental pathway. 36-44 Upon skeletal injury, however, even 2-year-old animals were capable of mounting a chondrogenic response ( Fig. 7 ); accordingly, this strain may prove useful in evaluating treatments that alter key hallmarks of aging to enhance chondrogenesis and facilitate cartilage repair in aged joints.…”

Section: Discussionmentioning

confidence: 99%

A Transgenic Rat for Noninvasive Assessment of Chondrogenesis in Vivo

et al. 2021

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Objective To support the preclinical evaluation of therapeutics that target chondrogenesis, our goal was to generate a rat strain that can noninvasively report endogenous chondrogenic activity. Design A transgene was constructed in which the dual expression of bioluminescent (firefly luciferase) and fluorescent (mCherry) reporters is controlled by regulatory sequences from rat Col2a1. Candidate lines were established on a Lewis background and characterized by serial bioluminescence imaging as well as ex vivo measurement of molecular reporter levels in several tissues. The sensitivity and specificity of the reporter strain were assessed in models of orthotopic and ectopic chondrogenesis. Results Substantial bioluminescence signal was detected from cartilaginous regions, including the appendicular synovial joints, spine, sternum, nose, and pinnae. Bioluminescent radiance was intense at 1 month of age, rapidly declined with continued development, yet remained detectable in 2-year-old animals. Explant imaging and immunohistochemistry confirmed that both molecular reporters were localized to cartilage. Implantation of wild-type bone marrow stromal cells into osteochondral defects made in both young adult and aged reporter rats led to a time-dependent elevation of intra-articular reporter activity concurrent with cartilaginous tissue repair. To stimulate ectopic, endochondral bone formation, bone morphogenetic protein 2 was overexpressed in the gastrocnemius muscle, which led to bioluminescent signal that closely preceded heterotopic ossification. Conclusions This strain can help develop strategies to stimulate cartilage repair and endochondral bone formation or to inhibit chondrogenesis associated with heterotopic ossification.

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“…All samples were snap‐frozen in liquid nitrogen before being stored at −80°C until further use. RNA isolation, reverse transcription, and quantitative PCR were all conducted as previously described 27 . Expression of anabolic tissue synthesis genes Col2, Col1, Col10, ACAN, and SOX9, and catabolic enzyme genes ADAMTS4 and ADAMTS5 were analyzed via custom primers, designed as previously described 27 .…”

Section: Methodsmentioning

confidence: 99%

“…27 Expression of anabolic tissue synthesis genes Col2, Col1, Col10, ACAN, and SOX9, and catabolic enzyme genes ADAMTS4 and ADAMTS5 were analyzed via custom primers, designed as previously described. 27 Gene expression data (C T ) were standardized to the expression of the housekeeping gene PPIA (ΔC T ) and calculated as fold change 2 -C T ∆∆ from the average gene expression of the control group. PPIA was selected as a housekeeping gene because of its stability in our model.…”

Section: Metabolic Inhibition and Gene Expression Analysismentioning

confidence: 99%

Maturation‐ and degeneration‐dependent articular cartilage metabolism via optical redox ratio imaging

Walsh

Soni

Arendt

et al. 2021

Journal Orthopaedic Research

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From the two metabolic processes in healthy cartilage, glycolysis has been associated with proliferation and oxidative phosphorylation (oxphos) with matrix synthesis. Recently, metabolic dysregulation was significantly correlated with cartilage degradation and osteoarthritis progression. While these findings suggest maturation predisposes cartilage to metabolic instability with consequences for tissue maintenance, these links have not been shown. Therefore, this study sought to address three hypotheses (a) chondrocytes exhibit differential metabolic activity between immaturity (0–4 months), adolescence (5–18 months), and maturity (>18 months); (b) perturbation of metabolic activity has consequences on expression of genes pertinent to cartilage tissue maintenance; and (c) severity of cartilage damage is positively correlated with glycolysis and oxphos activity as well as optical redox ratio in postadolescent cartilage. Porcine femoral cartilage samples from pigs (3 days to 6 years) underwent optical redox ratio imaging, which measures autofluorescence of NAD(P)H and FAD. Gene expression analysis and histological scoring was conducted for comparison against imaging metrics. NAD(P)H and FAD autofluorescence both demonstrated increasing intensity with age, while optical redox ratio was lowest in adolescent samples compared to immature or mature samples. Inhibition of glycolysis suppressed expression of Col2, Col1, ADAMTS4, and ADAMTS5, while oxphos inhibition had no effect. FAD fluorescence and optical redox ratio were positively correlated with histological degeneration. This study demonstrates maturation‐ and degeneration‐dependent metabolic activity in cartilage and explores the consequences of this differential activity on gene expression. This study aids our basic understanding of cartilage biology and highlights opportunity for potential diagnostic applications.

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Maturity-dependent cartilage cell plasticity and sensitivity to external perturbation

Cited by 7 publications

References 51 publications

The clinical potential of articular cartilage-derived progenitor cells: a systematic review

The clinical potential of articular cartilage-derived progenitor cells: a systematic review

A Transgenic Rat for Noninvasive Assessment of Chondrogenesis in Vivo

Maturation‐ and degeneration‐dependent articular cartilage metabolism via optical redox ratio imaging

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