scholarly journals Cartilage Protective and Chondrogenic Capacity of WIN-34B, a New Herbal Agent, in the Collagenase-Induced Osteoarthritis Rabbit Model and in Progenitor Cells from Subchondral Bone

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Jeong-Eun Huh ◽  
Yeon-Cheol Park ◽  
Byung-Kwan Seo ◽  
Jae-Dong Lee ◽  
Yong-Hyeon Baek ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Cartilage Repair ◽  
Subchondral Bone ◽  
Chondrogenic Differentiation ◽  
Rabbit Model ◽  
Type Ii Collagen ◽  
Blue Staining ◽  
Vehicle Group ◽  
Potential Candidate ◽  
Type Ii

We sought to determine the cartilage repair capacity of WIN-34B in the collagenase-induced osteoarthritis rabbit model and in progenitor cells from subchondral bone. The cartilage protective effect of WIN-34B was measured by clinical and histological scores, cartilage area, and proteoglycan and collagen contents in the collagenase-induced osteoarthritis rabbit model. The efficacy of chondrogenic differentiation of WIN-34B was assessed by expression of CD105, CD73, type II collagen, and aggrecanin vivoand was analyzed by the surface markers of progenitor cells, the mRNA levels of chondrogenic marker genes, and the level of proteoglycan, GAG, and type II collagenin vitro. Oral administration of WIN-34B significantly increased cartilage area, and this was associated with the recovery of proteoglycan and collagen content. Moreover, WIN-34B at 200 mg/kg significantly increased the expression of CD105, CD73, type II collagen, and aggrecan compared to the vehicle group. WIN-34B markedly enhanced the chondrogenic differentiation of CD105 and type II collagen in the progenitor cells from subchondral bone. Also, we confirmed that treatment with WIN-34B strongly increased the number of SH-2(CD105) cells and expression type II collagen in subchondral progenitor cells. Moreover, WIN-34B significantly increased proteoglycan, as measured by alcian blue staining; the mRNA level of type IIα1 collagen, cartilage link protein, and aggrecan; and the inhibition of cartilage matrix molecules, such as GAG and type II collagen, in IL-1β-treated progenitor cells. These findings suggest that WIN-34B could be a potential candidate for effective anti-osteoarthritic therapy with cartilage repair as well as cartilage protection via enhancement of chondrogenic differentiation in the collagenase-induced osteoarthritis rabbit model and progenitor cells from subchondral bone.

Morphological Assessment of MACI Grafts in Patients with Revision Surgery and Total Joint Arthroplasty

Cartilage ◽  
2019 ◽  
pp. 194760351989075 ◽  
Author(s):  
Aswin Beck ◽  
David Wood ◽  
Christopher J. Vertullo ◽  
Jay Ebert ◽  
Greg Janes ◽  
...  
Keyword(s):  
Cartilage Repair ◽  
Subchondral Bone ◽  
Revision Surgery ◽  
Total Joint Arthroplasty ◽  
Type Ii Collagen ◽  
Joint Arthroplasty ◽  
Type I ◽  
Type Ii ◽  
Osteophyte Formation ◽  
Repair Tissue

Objective To compare the histological and immunohistochemical characteristics of matrix-assisted chondrocyte implantation (MACI) grafts between patients with revision surgery and patients with total joint arthroplasty. Methods Biopsies of MACI grafts from patients with revision and total joint arthroplasty. The graft tissue characteristics and subchondral bone were examined by qualitative histology, ICRS (International Cartilage Repair Society) II scoring and semiquantitative immunohistochemistry using antibodies specific to type I and type II collagen. Results A total of 31 biopsies were available, 10 undergoing total knee arthroplasty (TKA) and 21 patients undergoing revision surgery. Patients in the clinically failed group were significantly older (46.3 years) than patients in the revision group (36.6 years) ( P = 0.007). Histologically, the predominant tissue in both groups was of fibrocartilaginous nature, although a higher percentage of specimens in the revision group contained a hyaline-like repair tissue. The percentages of type I collagen (52.9% and 61.0%) and type II collagen (66.3% and 42.2%) were not significantly different between clinically failed and revised MACI, respectively. The talar dome contained the best and patella the worst repair tissue. Subchondral bone pathology was present in all clinically failed patients and consisted of bone marrow lesions, including edema, necrosis and fibrosis, intralesional osteophyte formation, subchondral bone plate elevation, intralesional osteophyte formation, subchondral bone cyst formation, or combinations thereof. Conclusions MACI grafts in patients with revision and total joint arthroplasty were predominantly fibrocartilage in repair type, did not differ in composition and were histologically dissimilar to healthy cartilage. Clinically failed cases showed evidence of osteochondral unit failure, rather than merely cartilage repair tissue failure. The role of the subchondral bone in relation to pain and failure and the pathogenesis warrants further investigation.

scholarly journals Combination of collagen scaffold with doxycycline for the treatment of cartilage and subchondral bone defects

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Haixiang Liang ◽  
Spencer Stein ◽  
Pooja Swami ◽  
Henintsoa Fanjaniaina ◽  
Daniel Grande
Keyword(s):  
Cartilage Repair ◽  
Subchondral Bone ◽  
Tissue Repair ◽  
Bone Repair ◽  
Type Ii Collagen ◽  
Cartilage Tissue ◽  
Type I ◽  
Type Ii ◽  
Collagen Production

The repair of cartilage and bone tissue post arthritis or injury in the knee joint is a challenge to the orthopedics. Both doxycycline and collagen scaffolds had been shown with positive influences on the repair of the tissue. Doxycycline inhibits catabolism related enzymes. Collagens provide tissue repair materials. In this study, the influence of doxycycline and jellyfish collagen (JFC) scaffold to the cells in vitro and tissue repair in vivo was studied. Doxycycline was found with a broad inhibition of the matrix metallopeptidases. It also had an enhancement to the progenitor chondrocytes but suppressed the maturation of chondrocytes. JFC (major type II collagen) was seen had improved both type I and type II collagen production during chondrogenesis of mesenchymal stem cells in vitro. Both doxycycline and JFC enhanced the bone formation and had synergistic effects in a late-stage during the bone repair process. However, the cartilage repair was found with no significant influence after the implantations. Overall, the control of metabolism by doxycycline and providing stimulation to collagen production by the implantation of JFC only contribute to bone growth but had little influence on cartilage repair. This indicates the growth of cartilage tissue needs more delicate regulation. The subchondral bone repair, even with some chondrocytes and proteoglycan deposition in the extracellular matrix could not convert to a repair with mature hyaluronic cartilage tissue.

Healing of Circular Defects in the Rabbit Medial Meniscus Can Occur Spontaneously and Is not Improved by Intra-Articular Hyaluronic Acid

1996 ◽  
Vol 09 (02) ◽  
pp. 60-5 ◽  
Author(s):  
N. Hope ◽  
P. Ghosh ◽  
S. Collier
Keyword(s):  
Hyaluronic Acid ◽  
Medial Meniscus ◽  
Chondroitin Sulphate ◽  
Rabbit Model ◽  
Type Ii Collagen ◽  
Type Ii ◽  
Keratan Sulphate ◽  
Meniscal Healing ◽  
Meniscus Healing ◽  
Made In

SummaryThe aim of this study was to determine the effects of intra-articular hyaluronic acid on meniscal healing. Circular defects, 1.0 mm in diameter, were made in the anterior third of the medial meniscus in rabbits. In one joint, 0.4 ml hyaluronic acid (Healon®) was instilled, and in the contralateral (control) joint, 0.4 ml Ringer’s saline. Four rabbits were killed after four, eight and 12 weeks and the menisci examined histologically. By eight weeks most of the lesions had healed by filling with hyaline-like cartilage. Healing was not improved by hyaluronic acid treatment. The repair tissue stained strongly with alcian blue, and the presence of type II collagen, keratan sulphate, and chondroitin sulphate was demonstrated by immunohistochemical localisation. In contrast to the circular defects, longitudinal incisions made in the medial menisci of a further six rabbits did not show any healing after 12 weeks, indicating that the shape of the lesion largely determined the potential for healing.The effect of hyaluronic acid on meniscal healing was tested in a rabbit model. With one millimeter circular lesions in the medial meniscus, healing by filling with hyalinelike cartilage was not significantly affected by the application of hyaluronic acid intra-articularly at the time of surgery, compared to saline controls, as assessed histologically four, eight and 12 weeks after the operation.

scholarly journals FOXO1 transcription factor regulates chondrogenic differentiation through transforming growth factor β1 signaling

2019 ◽  
Vol 294 (46) ◽  
pp. 17555-17569 ◽  
Author(s):  
Ichiro Kurakazu ◽  
Yukio Akasaki ◽  
Mitsumasa Hayashida ◽  
Hidetoshi Tsushima ◽  
Norio Goto ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Growth Factor ◽  
Cell Cycle Arrest ◽  
Chondrogenic Differentiation ◽  
Transforming Growth Factor ◽  
Human Mesenchymal Stem Cells ◽  
Type Ii Collagen ◽  
Transforming Growth Factor Β1 ◽  
Type Ii ◽  
Cycle Arrest

The forkhead box O (FOXO) proteins are transcription factors involved in the differentiation of many cell types. Type II collagen (Col2) Cre-Foxo1-knockout and Col2-Cre-Foxo1,3,4 triple-knockout mice exhibit growth plate malformation. Moreover, recent studies have reported that in some cells, the expressions and activities of FOXOs are promoted by transforming growth factor β1 (TGFβ1), a growth factor playing a key role in chondrogenic differentiation. Here, using a murine chondrogenic cell line (ATDC5), mouse embryos, and human mesenchymal stem cells, we report the mechanisms by which FOXOs affect chondrogenic differentiation. FOXO1 expression increased along with chondrogenic differentiation, and FOXO1 inhibition suppressed chondrogenic differentiation. TGFβ1/SMAD signaling promoted expression and activity of FOXO1. In ATDC5, FOXO1 knockdown suppressed expression of sex-determining region Y box 9 (Sox9), a master regulator of chondrogenic differentiation, resulting in decreased collagen type II α1 (Col2a1) and aggrecan (Acan) expression after TGFβ1 treatment. On the other hand, chemical FOXO1 inhibition suppressed Col2a1 and Acan expression without suppressing Sox9. To investigate the effects of FOXO1 on chondrogenic differentiation independently of SOX9, we examined FOXO1's effects on the cell cycle. FOXO1 inhibition suppressed expression of p21 and cell-cycle arrest in G0/G1 phase. Conversely, FOXO1 overexpression promoted expression of p21 and cell-cycle arrest. FOXO1 inhibition suppressed expression of nascent p21 RNA by TGFβ1, and FOXO1 bound the p21 promoter. p21 inhibition suppressed expression of Col2a1 and Acan during chondrogenic differentiation. These results suggest that FOXO1 is necessary for not only SOX9 expression, but also cell-cycle arrest during chondrogenic differentiation via TGFβ1 signaling.

Facilitating In Vivo Articular Cartilage Repair by Tissue-Engineered Cartilage Grafts Produced From Auricular Chondrocytes

2017 ◽  
Vol 46 (3) ◽  
pp. 713-727 ◽  
Author(s):  
Chin-Chean Wong ◽  
Chih-Hwa Chen ◽  
Li-Hsuan Chiu ◽  
Yang-Hwei Tsuang ◽  
Meng-Yi Bai ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Articular Cartilage ◽  
Cartilage Repair ◽  
Articular Chondrocytes ◽  
Type Ii Collagen ◽  
Type Ii ◽  
Articular Cartilage Repair ◽  
3 Dimensional ◽  
Cell Conversion

Background: Insufficient cell numbers still present a challenge for articular cartilage repair. Converting heterotopic auricular chondrocytes by extracellular matrix may be the solution. Hypothesis: Specific extracellular matrix may convert the phenotype of auricular chondrocytes toward articular cartilage for repair. Study Design: Controlled laboratory study. Methods: For in vitro study, rabbit auricular chondrocytes were cultured in monolayer for several passages until reaching status of dedifferentiation. Later, they were transferred to chondrogenic type II collagen (Col II)–coated plates for further cell conversion. Articular chondrogenic profiles, such as glycosaminoglycan deposition, articular chondrogenic gene, and protein expression, were evaluated after 14-day cultivation. Furthermore, 3-dimensional constructs were fabricated using Col II hydrogel-associated auricular chondrocytes, and their histological and biomechanical properties were analyzed. For in vivo study, focal osteochondral defects were created in the rabbit knee joints, and auricular Col II constructs were implanted for repair. Results: The auricular chondrocytes converted by a 2-step protocol expressed specific profiles of chondrogenic molecules associated with articular chondrocytes. The histological and biomechanical features of converted auricular chondrocytes became similar to those of articular chondrocytes when cultivated with Col II 3-dimensional scaffolds. In an in vivo animal model of osteochondral defects, the treated group (auricular Col II) showed better cartilage repair than did the control groups (sham, auricular cells, and Col II). Histological analyses revealed that cartilage repair was achieved in the treated groups with abundant type II collagen and glycosaminoglycans syntheses rather than elastin expression. Conclusion: The study confirmed the feasibility of applying heterotopic chondrocytes for cartilage repair via extracellular matrix–induced cell conversion. Clinical Relevance: This study proposes a feasible methodology to convert heterotopic auricular chondrocytes for articular cartilage repair, which may serve as potential alternative sources for cartilage repair.

Differentiation and Immunoregulatory Activity of Dental Pulp-Derived Mesenchymal Cells.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4245-4245
Author(s):  
Alberto Grossi ◽  
Laura Pierdomenico ◽  
Laura Bonsi ◽  
Cosetta Marchionni ◽  
Francesco Alviano ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
T Lymphocyte ◽  
Dental Pulp ◽  
Lymphocyte Proliferation ◽  
Chondrogenic Differentiation ◽  
Flow Cytometric Analysis ◽  
Type Ii Collagen ◽  
Type Ii ◽  
T Lymphocyte Proliferation

Abstract INTRODUCTION. Mesenchymal Stem Cells (MSC) have the ability to renew and differentiate into various lineages of mesenchymal tissue such as bone, cartilage, fat, muscle, etc. Moreover they are not immunogenic and display immunoregulatory activity in preclinical animal models. The aim of this study was to investigate whether dental pulp MSC (DPMSC) were able to differentiate toward osteogenesis, chondrogenesis and adipogenesis and express the characteristic immunomodulatory activity of MSC derived from known sources such as bone marrow. METHODS and RESULTS. We isolated MSC from dental pulp and bone marrow samples obtained from fully informed healthy donors. Flow cytometric analysis showed that either DPMSC or bone marrow MSC (BMMSC) expressed the membrane antigens SH2, SH3, SH4, CD29 and CD166, while CD 14, CD 34 and CD 45 were negative. Cell differentiation was evaluated after PDMSC and BMMSC were cultured in appropriate conditions. To evaluate adipogenesis after 2–3 weeks of culture the cells, containing neutral lipids in fat vacuoles, were fixed in 10% formalin and stained with fresh oil red-O solution. To demonstrate osteogenic differentiation, the cultures were fixed and subjected to alkaline phosphatase and von Kossa staining. For chondrogenic differentiation pellets were formalin fixed, embedded in paraffin, examined morphologically and immunostained for Type II collagen. We observed that either PDMSC and BMMSC were able to express clear osteogenic and chondrogenic differentiation as demonstrated by von Kossa staining and Type II collagen immunostaining respectively, but a lower number of adipocytes was obtained, according to morphology and red-oil staining, in DPMSC cultures. For proliferation assay cells were incubated overnight, then [methyl-3H] Thymidine was added (Time 0) and radioactivity followed for up to 15 days. DPMSC and BMMSc presented a very different behaviour in that DPMSC radioactivity had a steep increase from day 3 to 8, then decreasing at day 15, although still above the baseline value. On the contrary BMMSC radioactivity did not change significantly over the time of observation. Modulation of T Lymphocyte proliferation was studied by coculturing PHA stimulated T cells in the presence of MSC. Compared to cultures of T cells alone, the uptake of [methyl-3H] Thymidine was inhibited by 75%±3%(BMMSC)or 91%±4% (DPMSC). CONCLUSIONS: Dental pulp is a source of cells expressing the typical phenotype of MSC. Compared to BMMSC, DPMSC present a higher rate of proliferating cells (S-phase), and lower differentiation capabilities toward adipogenesis. These results suggest that BMMSC and DPMSCs are present at diverse differentiation stages, possibly not evidenced by phenotypic characteristics, and their plasticity in different experimental conditions should be further investigated. DPMSC are able to suppress stimulated T lymphocyte proliferation, as described for BMMSC. Therefore they are good candidates when modulation of T cell activity is required, as shown recently by Le Blanc (2003) in the treatment of GVHD in allogeneic transplantation setting.

scholarly journals The Mechanism for Type II Collagen in Modulating Osteochondral Differentiation of Mesenchymal Progenitor Cells

2009 ◽  
Vol 23 (S1) ◽  
Author(s):  
Li‐Hsuan Chiu ◽  
Charng‐Bin Yang ◽  
Chia‐Lang Fang ◽  
Wen‐Fu T Lai ◽  
Yu‐Wei Wu ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Type Ii Collagen ◽  
Type Ii ◽  
Mesenchymal Progenitor Cells
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