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Introduction. Elevated remodelling of subchondral bone and marrow tissues has been firmly established as diagnostic and prognostic radiological imaging marker for human osteoarthritis. While these tissues are considered as promising targets for disease-modifying OA drugs, the development of novel treatment approaches is complicated by the lack of knowledge whether similar tissue changes occur in rodent OA models and poor understanding of joint-specific molecular and cellular pathomechanisms in human OA. Here, we describe the establishment of a human OA explant model to address this crucial niche in translational preclinical OA research. Methods. Osteochondral (knee, spine) and bone (iliac crest) clinical specimens were acquired from patients undergoing total knee arthroplasty (n=4) or lumbar spine fusion using bone autografts (n=6). Fresh specimens were immediately cut in equal-sized samples (50–500 mg wet weight) and cultured in 8 mL osteogenic medium for one week. Samples were either left untreated (control) or stimulated with lipopolysaccharide (LPS, 100 ng/mL) in the absence and presence of transforming growth factor-beta inhibitor (SB-505124, 10 μm). Pro-collagen-I (Col-I), interleukin-6 (IL-6) and monocyte chemoattractant protein 1 (MCP-1) secretion was determined in conditioned medium by ELISA. Tissue viability was assessed using MTT and alkaline phosphatase (ALP) activity staining. Results. Explanted tissues remained viable after one week culture in control and treatment conditions. Osteocytes, subchondral marrow spaces and calcified cartilage stained positive for ALP activity without gross morphological differences between groups. Median basal secretion levels were Col-I (2.3 ng/mg), IL-6 (90 pg/mg) and MCP-1 (25 pg/mg). LPS treatment led to a significant increase of IL-6 (330 pg/mg) and MCP-1 (70 pg/mg), but not Col-I secretion. Interestingly, inhibition of TGF-beta signalling in osteochondral tissues specifically reduced Col-I levels (0.4 ng/mg) compared to controls and LPS-treated samples. LPS-induced IL-6 and MCP-1 levels were slightly reduced (−120 pg/mg, p=0.03) and increased (+50 pg/mg) by SB-505124 treatment, respectively. IL-6 and MCP-1 levels were strongly correlated under basal (r=0.80) and treatment conditions (r=0.62). Conclusion. In this study, we provided proof of concept for the first ex vivo explant model of human osteoarthritis. Osteochondral tissue specimens can readily be cultured without loss of tissue viability and mount a robust inflammatory response upon LPS challenge. Treatment with a potential
Louis Pasteur once said that: “Fortune favours
the prepared mind.” As one of the great scientists who contributed
to the fight against infection, he emphasised the importance of
being prepared at all times to recognise infection and deal with
it. Despite the many scientific discoveries and technological advances,
such as the advent of antibiotics and the use of sterile techniques,
infection continues to be a problem that haunts orthopaedic surgeons
and inflicts suffering on patients. The medical community has implemented many practices with the
intention of preventing infection and treating it effectively when
it occurs. Although high-level evidence may support some of these
practices, many are based on little to no scientific foundation.
Thus, around the world, there is great variation in practices for
the prevention and management of periprosthetic joint infection. This paper summaries the instigation, conduct and findings of
a recent International Consensus Meeting on Surgical Site and Periprosthetic
Joint Infection. Cite this article:
