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TGF-β1 as a prognostic factor in the process of early osteoarthrosis in the rabbit knee
Linköping University, Department of Neuroscience and Locomotion, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Neuroscience and Locomotion, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Neuroscience and Locomotion, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences.
2001 (English)In: Osteoarthritis and Cartilage, ISSN 1063-4584, E-ISSN 1522-9653, Vol. 9, no 3, 195-202 p.Article in journal (Refereed) Published
Abstract [en]

Objective To assess changes in knee joint fluid concentrations of transforming growth factor-β1 (TGF-β1) and proteoglycan (PG) fragments during the early course of post-traumatic osteoarthrosis (OA) after meniscectomy in the rabbit knee, and to ascertain whether the concentrations of these substances shortly after operation could be used as prognostic markers for the OA process.

Design In 15 rabbits with medial meniscectomy in one knee and a sham operation in the other knee, synovial lavage fluid samples were taken repeatedly, before operation, every third week post-operatively until 12 weeks, thereafter every sixth week, and at death. Five rabbits each were killed at 13, 25 and 40 weeks. Synovial lavage fluid samples from five non-operated rabbits served as controls. At death, two histological scores were formed that characterized the highest (MAX) and the overall (ALL) degree of OA changes in each joint.

Results TGF-β1 and PG fragment concentrations in synovial lavage fluid correlated highly (R=0.81, P< 0.001). Both OA scores were higher in meniscectomized than controls (P< 0.05). The synovial lavage fluid concentration of TGF-β1 at 3 weeks, but no other time point, correlated to the histological scores (ALL, R=0.58; MAX, R=0.52;P< 0.001).

Conclusion Higher concentrations of TGF-β1 in synovial lavage fluid early after surgery seemed indicative for the later development of more severe OA changes in contrast to lower concentrations. The association between TGF-β1 and the changes found later in the cartilage was underlined by the high correlations between this substance and PG fragment concentrations in synovial lavage fluid at all time points.

Place, publisher, year, edition, pages
2001. Vol. 9, no 3, 195-202 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-27601DOI: 10.1053/joca.2000.0376Local ID: 12331OAI: oai:DiVA.org:liu-27601DiVA: diva2:248153
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2012-10-10Bibliographically approved
In thesis
1. Early knee osteoarthrosis after meniscectomy: studies in rabbits
Open this publication in new window or tab >>Early knee osteoarthrosis after meniscectomy: studies in rabbits
2003 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Post-traumatic osteoarthrosis develops after intraarticular injuries. It is a disease, which affects both articular cartilage and subchondral bone, and progresses over 10-20 years. Irreversible damage has often occurred by the time clinical diagnosis is possible. More knowledge about the early phase of the disease might yield measures to detect and delay or even prevent progression. This thesis evaluates changes in articular cartilage and subchondral bone at an early stage of post-traumatic osteoarthrosis.

Simultaneous changes in articular cartilage and subchondral bone were evaluated 3 to 40 weeks post-operatively in a rabbit meniscectomy model for post-traumatic osteoarthrosis. Rabbits were meniscectomized in the right knee and sham-operated in the left knee. Osteoarthrotic cartilage changes were evaluated by histology. Changes in the subchondral bone were evaluated by histology, scintimetry and dual-energy X-ray absorptiometry (DEXA). Joint space narrowing, and its utility as diagnostic tool at early stages of osteoarthrosis, was assessed with weight-bearing radiographs. The prognostic value of transforming growth factor-ßI (TGF-ß1) and proteoglycan fragment concentrations in the joint fluid at an early stage was also assessed.

We found slight cartilage changes and an increased metabolic activity in the subchondral bone as early as 3 weeks after meniscectomy. However, sham-operated knees displayed similar changes, although to a lesser degree. Cartilage fibrillation progressed at areas of high load within the meniscectomized knee joint. The subchondral bone showed a general response such as high scintimetric activity 3 weeks after surgery, and a decreased bone mineral density at later time points. Local adaptation in areas of high load within the subchondral bone was also seen. There was an increased osteoid content at the border between the cancellous bone and the marrow cavity already 3 weeks after meniscectomy, and at 13 weeks the subchondral bone plate was thickened. This thickening of the bone plate persisted up to 40 weeks. Joint space narrowing occurred after removal of the meniscus, but weight-bearing radiographs were not sensitive enough to measure early cartilage changes. Increased concentration of TGF-ß1 in the joint fluid at 3 weeks after surgery was associated with a higher degree of histological osteoarthrotic changes at a later time point.

Simultaneous changes in both cartilage and bone were apparent already 3 weeks after surgery, indicating that both tissues are involved from a very early stage. The localisation of cartilage changes illustrates that mechanical consequences of meniscectomy play a crucial role in progression of the disease. Surgical trauma resulted in increased release of TGF-ß1 at 3 weeks after surgery. This was found to be indicative for the severity of later osteoarthrosis. Thus, factors solely associated with the surgical trauma may also be important for the progression of osteoarthrosis.

Place, publisher, year, edition, pages
Linköping: Linköpings universitet, 2003. 55 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 795
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-28031 (URN)12791 (Local ID)91-7373-553-1 (ISBN)12791 (Archive number)12791 (OAI)
Public defence
2003-06-05, Elsa Brändströms sal, Hälsouniversitet, Linköping, 13:00 (Swedish)
Opponent
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2012-10-10Bibliographically approved

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Fahlgren, AnnaAndersson, Britt-MarieMessner, Karola

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