scholarly journals Adult chondrogenesis and spontaneous cartilage repair in the skate, Leucoraja erinacea

2019 ◽  
Author(s):  
Aleksandra Marconi ◽  
Amy Hancock-Ronemus ◽  
J. Andrew Gillis

Mammalian articular cartilage is an avascular tissue with poor capacity for spontaneous repair. Here, we show that embryonic development of cartilage in the skate (Leucoraja erinacea) mirrors that of mammals, with developing chondrocytes co-expressing genes encoding the transcription factors Sox5, Sox6 and Sox9. However, in skate, transcriptional features of developing cartilage persist into adulthood, both in peripheral chondrocytes and in cells of the fibrous perichondrium that ensheaths the skeleton. Using pulse-chase label retention experiments and multiplexed in situ hybridization, we identify a population of cycling Sox5/6/9+ perichondral progenitor cells that generate new cartilage during adult growth, and we show that persistence of chondrogenesis in adult skates correlates with ability to spontaneously repair cartilage injuries. Skates therefore offer a unique model for adult chondrogenesis and cartilage repair and may serve as inspiration for novel cell-based therapies for skeletal pathologies, such as osteoarthritis.

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Aleksandra Marconi ◽  
Amy Hancock-Ronemus ◽  
J Andrew Gillis

Mammalian articular cartilage is an avascular tissue with poor capacity for spontaneous repair. Here, we show that embryonic development of cartilage in the skate (Leucoraja erinacea) mirrors that of mammals, with developing chondrocytes co-expressing genes encoding the transcription factors Sox5, Sox6 and Sox9. However, in skate, transcriptional features of developing cartilage persist into adulthood, both in peripheral chondrocytes and in cells of the fibrous perichondrium that ensheaths the skeleton. Using pulse-chase label retention experiments and multiplexed in situ hybridization, we identify a population of cycling Sox5/6/9+ perichondral progenitor cells that generate new cartilage during adult growth, and we show that persistence of chondrogenesis in adult skates correlates with ability to spontaneously repair cartilage injuries. Skates therefore offer a unique model for adult chondrogenesis and cartilage repair and may serve as inspiration for novel cell-based therapies for skeletal pathologies, such as osteoarthritis.


2020 ◽  
Vol 15 (9) ◽  
pp. 2129-2142
Author(s):  
Jun Zhang ◽  
Ziming Liu ◽  
Yuwan Li ◽  
Qi You ◽  
Jibin Yang ◽  
...  

Ligament/tendon and cartilage injuries are clinically common diseases that perplex most clinicians. Because of the lack of blood vessels and nerves, their self-repairing abilities are rather poor. Therefore, surgeries are necessary and also widely used to treat ligament/tendon or cartilage injuries. However, after surgery, there are still many problems that affect healing. In recent years, it has been found that exogenous FGF2 plays an important role in the repair of ligament/tendon and cartilage injuries and exerts a synergistic effect with endogenous FGF2. Therefore, FGF2 can be used as a new type of biomolecule to accelerate tendon-to-bone healing and cartilage repair after injury.


Author(s):  
Le Cao ◽  
Yuling Tong ◽  
Xiao Wang ◽  
Qiang Zhang ◽  
Yiying Qi ◽  
...  

Objectives: Repairing articular cartilage damage is challenging. Clinically, tissue engineering technology is used to induce stem cell differentiation and proliferation on biological scaffolds to repair defective joints. However, no ideal biological scaffolds have been identified. This study investigated the effects of amniotic membrane/collagen scaffolds on the differentiation of adipose-derived stem cells (ADSCs) and articular cartilage repair.Methods: Adipose tissue of New Zealand rabbits was excised, and ADSCs were isolated and induced for differentiation. An articular cartilage defect model was constructed to identify the effect of amniotic membrane/collagen scaffolds on cartilage repair. Cartilage formation was analyzed by imaging and toluene blue staining. Knee joint recovery in rabbits was examined using hematoxylin and eosin, toluidine, safranine, and immunohistochemistry at 12 weeks post-operation. Gene expression was examined using ELISA, RT-PCR, Western blotting, and immunofluorescence.Results: The adipose tissue was effectively differentiated into ADSCs, which further differentiated into chondrogenic, osteogenic, and lipogenic lineages after 3 weeks’ culture in vitro. Compared with platelet-rich plasmon (PRP) scaffolds, the amniotic membrane scaffolds better promoted the growth and differentiation of ADSCs. Additionally, scaffolds containing the PRP and amniotic membrane efficiently enhanced the osteogenic differentiation of ADSCs. The levels of COL1A1, COL2A1, COL10A1, SOX9, and ACAN in ADSCs + amniotic membrane + PRP group were significantly higher than the other groups both in vitro and in vivo. The Wakitani scores of the ADSC + amniotic membrane + PRP group were lower than that in ADSC + PRP (4.4 ± 0.44**), ADSC + amniotic membrane (2.63 ± 0.38**), and control groups (6.733 ± 0.21) at week 12 post-operation. Osteogenesis in rabbits of the ADSC + amniotic membrane + PRP group was significantly upregulated when compared with other groups. Amniotic membranes significantly promoted the expression of cartilage regeneration-related factors (SOX6, SOX9, RUNX2, NKX3-2, MEF2C, and GATA4). The ADSC + PRP + amniotic membrane group exhibited the highest levels of TGF-β, PDGF, and FGF while exhibiting the lowest level of IL-1β, IL6, and TNF-α in articular cavity.Conclusion: Amniotic membrane/collagen combination-based scaffolds promoted the proliferation and cartilage differentiation of ADSCs, and may provide a new treatment paradigm for patients with cartilage injury.


2008 ◽  
Vol 14 (7) ◽  
pp. 1133-1140 ◽  
Author(s):  
Dana L. Nettles ◽  
Kenichi Kitaoka ◽  
Neil A. Hanson ◽  
Charlene M. Flahiff ◽  
Brian A. Mata ◽  
...  

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1052.1-1052
Author(s):  
S. Eldridge ◽  
A. Barawi ◽  
H. Wang ◽  
A. Roelofs ◽  
M. Kaneva ◽  
...  

Background:Cartilage defects in the joints are reported in 61% of all arthroscopies1&2. The size of the cartilage repair market is estimated to be $2.195 million by 20253. Cartilage defects can evolve into osteoarthritis, in which abnormal load results in cartilage breakdown, joint pain and reduced mobility. Osteoarthritis is the leading cause of permanent disability and absenteeism and affects up to 1/3 of the people over 60yrs. In western countries osteoarthritis costs 1.5-2% of the GDP4. Joint replacement with a prosthesis restores some degree of independence but in up to 20% of patients it does not meet expectations 5 and has a limited life span. There is no pharmacological intervention that arrests or reverts the course of osteoarthritis, despite the desperate need.We previously published that agrin plays an important role in cartilage homeostasis6. The addition of agrin to chondrocytes in vivo resulted in enhanced cartilage formation, suggesting a potential role for agrin in cartilage repair.Objectives:Investigate the potential of agrin for use in cartilage repair.Methods:Critical size osteochondral defects were generated in mice and sheep and injected intraarticularly with type I collagen gel containing agrin or vehicle. Animals were monitored for 8 weeks or 6 months respectively. MicroCT, histological analysis, qPCR, linage tracking, reporter assays, chondrogenesis assay, immunohistochemistry were performed.Results:A single intraarticular administration of agrin induced regeneration of critical-size osteochondral defects in mice, restoring the tissue architecture and bone-cartilage interface. Agrin stem cells to the site of injury and, through simultaneous activation of CREB and suppression of canonical WNT signalling, induced GDF5 expression and differentiation into stable articular chondrocytes, forming stable articular cartilage. In sheep, agrin treatment resulted in regeneration of bone and cartilage, which promoted increased ambulatory activity.Conclusion:Agrin orchestrates repair morphogenesis at the joint surface by modulating multiple signalling pathways, supporting the therapeutic use of agrin for joint surface regeneration.References:[1]Curl, W. W. et al. Cartilage injuries: a review of 31,516 knee arthroscopies. Arthrosc. J. Arthrosc. Relat. Surg. Off. Publ. Arthrosc. Assoc. N. Am. Int. Arthrosc. Assoc. 13, 456–460 (1997).[2]Hjelle, K., Solheim, E., Strand, T., Muri, R. & Brittberg, M. Articular cartilage defects in 1,000 knee arthroscopies. Arthrosc. J. Arthrosc. Relat. Surg. Off. Publ. Arthrosc. Assoc. N. Am. Int. Arthrosc. Assoc. 18, 730–734 (2002).[3]Cartilage Repair Market Size, Share, Industry Analysis 2018-2025 | AMR. Allied Market Research https://www.alliedmarketresearch.com/cartilage-repair-market.[4]Hiligsmann, M. et al. Health economics in the field of osteoarthritis: an expert’s consensus paper from the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO). Semin. Arthritis Rheum. 43, 303–313 (2013).[5]Dieppe, P., Lim, K. & Lohmander, S. Who should have knee joint replacement surgery for osteoarthritis? Int. J. Rheum. Dis. 14, 175–180 (2011).[6]Eldridge, S., et al. Agrin mediates chondrocyte homeostasis and requires both LRP4 and α-dystroglycan to enhance cartilage formation in vitro and in vivo. Annals of the rheumatic diseases 75 (6), 1228-1235 (2016).Acknowledgements:We thank the technical staff in the ARM Lab and Staff at the University of Aberdeen’s Animal Facility and Microscopy and Histology Facility for support. Funding: We gratefully acknowledge funding support of this work by the MRC (MR/L022893/1, MR/N010973/1,and MR/P026362/1), Versus Arthritis (19667, 21515, 20886, and 21621), Rosetrees Trust (A1205), the Medical College of St Bartholomew’s Hospital Trust, and the William Harvey Research Foundation.Disclosure of Interests:Suzanne Eldridge: None declared, Aida Barawi: None declared, Hui Wang: None declared, Anke Roelofs: None declared, Magdalena Kaneva: None declared, Zeyu Guan: None declared, Helen Lydon: None declared, Bethan Thomas: None declared, Anne-Sophie Thorup: None declared, Beatriz F Fernandez: None declared, Sara Caxaria: None declared, Danielle Strachan: None declared, Ahmed Ali: None declared, Kanatheepan Shanmuganathan: None declared, Costantino Pitzalis: None declared, James Whiteford: None declared, Fran Henson: None declared, Andrew McCaskie: None declared, Cosimo De Bari: None declared, Francesco Dell’Accio Consultant of: F.D. has received consultancy fees from Samumed and UCB.


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