Overexpression of active TGF-beta-1 in the murine knee joint: evidence for synovial-layer-dependent chondro-osteophyte formation

Bakker, Andrew C.; Loo, Fons A. J. van de; Beuningen, H.M. van; Sime, Patricia J.; Lent, P.L.E.M. van; Kraan, P.M. van der; Richards, Carl D.; Berg, Wim B. van den

doi:10.1053/joca.2000.0368

Cited by 279 publications

(198 citation statements)

References 35 publications

Supporting

Mentioning

181

Contrasting

Unclassified

Order By: Relevance

“…Active TGF␤ plays a key role in osteophyte formation (40). Furthermore, active TGF␤, injected into mouse knees or continuously overexpressed, leads to joint degeneration (41,42). Osteophyte formation was a prominent feature of OA seen in association with ascorbate in this study.…”

Section: Discussionmentioning

confidence: 50%

Ascorbic acid increases the severity of spontaneous knee osteoarthritis in a guinea pig model

Kraus

Huebner

Stäbler

et al. 2004

Arthritis & Rheumatism

View full text Add to dashboard Cite

Objective. To determine whether ascorbic acid might be of benefit for the treatment of spontaneous osteoarthritis (OA) when administered over a long period of time.Methods. We investigated the effects of 8 months' exposure to low, medium, and high doses of ascorbic acid on the in vivo development of histologic knee OA in the male Hartley guinea pig. The low dose represented the minimum amount needed to prevent scurvy. The medium dose was the amount present in standard laboratory guinea pig chow and resulted in plasma levels comparable with those achieved in a person consuming 200 mg/day (5 fruits and vegetables daily). The high dose was the amount shown in a previous study of the guinea pig to slow the progression of surgically induced OA.Results. We found an association between ascorbic acid supplementation and increased cartilage collagen content but, in contrast to findings in a previous study of surgically induced OA in the guinea pig, ascorbic acid worsened the severity of spontaneous OA. Active transforming growth factor ␤ (TGF␤) was expressed in marginal osteophytes, whose size and number were significantly increased with increasing intake of ascorbic acid. Synovial fluid levels of cartilage oligomeric matrix protein, a biomarker of cartilage turnover, corroborated the histologic findings.Conclusion. Ascorbic acid has been shown to activate latent TGF␤. Prolonged intraarticular exposure to TGF␤ has been shown to cause OA-like changes. We found expression of active TGF␤ in osteophytes, a prominent feature of the joint histology seen in association with ascorbic acid treatment. Thus, the deleterious effects of prolonged ascorbic acid exposure may be mediated in part by TGF␤. This worsening of OA with ascorbic acid supplementation suggests that ascorbic acid intake should not be supplemented above the currently recommended dietary allowance (90 mg/day for men and 75 mg/day for women).

show abstract

Section: Discussionmentioning

confidence: 50%

Ascorbic acid increases the severity of spontaneous knee osteoarthritis in a guinea pig model

Kraus

Huebner

Stäbler

et al. 2004

Arthritis & Rheumatism

View full text Add to dashboard Cite

show abstract

“…Given that many of the cDNAs considered to be candidates for this application such as TGF-b1 are pleiotropic, the movement of vector or genetically modified cells into the joint space could cause deleterious side effects within the joint such as fibrosis and ectopic bone formation. 31,32 It should be noted, however, that the CG matrix used in these experiments was not optimized for this method. It is likely that there are methods to incorporate vectors or genetic material more effectively into this scaffold that may provide improved containment and uniformity of gene transfer.…”

Section: Discussionmentioning

confidence: 99%

Gene delivery to cartilage defects using coagulated bone marrow aspirate

et al. 2004

View full text Add to dashboard Cite

The long-term goal of the present study is to develop a clinically applicable approach to enhance natural repair mechanisms within cartilage lesions by targeting bone marrow-derived cells for genetic modification. To determine if bone marrow-derived cells infiltrating osteochondral defects could be transduced in situ, we implanted collagen-glycosaminoglycan (CG) matrices preloaded with adenoviral vectors containing various marker genes into lesions surgically generated in rabbit femoral condyles. Analysis of the recovered implants showed transgenic expression up to 21 days; however, a considerable portion was found in the synovial lining, indicating leakage of the vector and/or transduced cells from the matrix. As an alternative medium for gene delivery, we investigated the feasibility of using coagulated bone marrow aspirates. Mixture of an adenoviral suspension with the fluid phase of freshly aspirated bone marrow resulted in uniform dispersion of the vector throughout, and levels of transgenic expression in direct proportion to the density of nucleated cells in the ensuing clot. Furthermore, cultures of mesenchymal progenitor cells, previously transduced ex vivo with recombinant adenovirus, were readily incorporated into the coagulate when mixed with fresh aspirate. These vector-seeded and cell-seeded bone marrow clots were found to maintain their structural integrity following extensive culture and maintained transgenic expression in this manner for several weeks. When used in place of the CG matrix as a gene delivery vehicle in vivo, genetically modified bone marrow clots were able to generate similarly high levels of transgenic expression in osteochondral defects with better containment of the vector within the defect. Our results suggest that coagulates formed from aspirated bone marrow may be useful as a means of gene delivery to cartilage and perhaps other musculoskeletal tissues. Cells within the fluid can be readily modified with an adenoviral vector, and the matrix formed from the clot is completely natural, native to the host and is the fundamental platform on which healing and repair of mesenchymal tissues is based.

show abstract

“…It has been suggested that osteophytes result from the abnormal healing response of subchondral trabeculae, or from the blood vessels penetration into the degrading cartilage [66]. It has been also shown that in OA the patient's osteophytes express TGF-β, which induces osteophyte formation in an experimental model [67,68]. Thomas et al [11] suggested that the action of leptin on bone tissue may be a result of bone marrow stromal cell stimulation and enhanced cell differentiation into osteoblasts with limited differentiation into adipocytes.…”

Section: Adipocytokines In Osteophyte Formationmentioning

confidence: 99%

The role of adipocytokines in the pathogenesis of knee joint osteoarthritis

Richter

Trzeciak

Owecki

et al. 2015

International Orthopaedics (SICOT)

View full text Add to dashboard Cite

Osteoarthritis (OA) is one of the most common causes of musculoskeletal disability in the world. Traditionally, it has been thought that obesity contributes to the development and progression of OA by increased mechanical load of the joint structures. Nevertheless, studies have shown that adipose tissue-derived cytokines (adipocytokines) are a possible link between obesity and OA. Furthermore, according to recent findings, not only articular cartilage may be the main target of these cytokines but also the synovial membrane, subchondral bone and infrapatellar fat pad may be encompassed in the process of degradation. This review presents the most recent reports on the contribution of adipocytokines to the knee joint cartilage degradation, osteophyte formation, infrapatellar fat pad alterations and synovitis.

show abstract

Overexpression of active TGF-beta-1 in the murine knee joint: evidence for synovial-layer-dependent chondro-osteophyte formation

Abstract: This study shows that overexpression of active TGF-beta1 in the knee joint results in OA-like changes and suggests the synovial lining cells contribute to the chondro-osteophyte formation.

Cited by 279 publications

References 35 publications

Ascorbic acid increases the severity of spontaneous knee osteoarthritis in a guinea pig model

Ascorbic acid increases the severity of spontaneous knee osteoarthritis in a guinea pig model

Gene delivery to cartilage defects using coagulated bone marrow aspirate

The role of adipocytokines in the pathogenesis of knee joint osteoarthritis

Contact Info

Product

Resources

About