cartilage damage and osteoarthritis

Using Mechanical Joint Loading Model to Investigate Knee Pathology and Nociceptive Behavior in OA

A very recent study 1 in the journal ‘Osteoarthritis and Cartilage’ has offered some helpful results. It focused on OA-induced pain in relation to mechanical joint loading and cartilage damage.

Why Conduct Such a Study?

Osteoarthritis or OA is defined as a degenerate joint disease that involves cartilage damage and the loss of cartilage. It tends to physically, emotionally, and economically impact numerous people around the world. And even though a lot still remains to be understood, progress has been made to look at osteoarthritis with a multifactorial lens.

Due to multiple joint tissues having identified pathologies as well as their relationship with OA, many have questioned the role pathologies play with regards to the clinical presentation of pain associated with OA.

When it comes to patients, the clinical presentation of their pain happens to be the most problematic oesteoarthritis symptom. And much remains unknown about knee pathology’s link with OA-related pain.

The current study’s primary objective was to better understand the complexities of the pain-structure relationship. The team used MJL or the mechanical joint loading model of OA for investigating knee pathology as well as nociceptive behavior.

What Was the Methodology?

The study used the MLJ model for inducing OA in the right knees of male mice. These mice were 12-weeks-old. A two-week loading regime was administered through an electronic testing machine.

A total of 36 mice had OA induced. Another batch of 36 mice (with no induced OA) acted as non-loaded controls. The team sacrificed separate groups of non-loaded and loaded mice during the one, three, and six-weeks points of post-loading for post-mortem analysis.

The study conducted behavior analysis before loading. At weeks one, three as well as six post-loading, nociception was verified (a day before the mentioned sacrifice points).

Coming to the post-mortem samples, half were used for µCT analysis, OA as well as synovitis grading. The other half ended up being used for nerve analysis.

The collected data was analyzed using the GraphPad Prism. Statistical analysis also included repeated two-way ANOVA, parametric two-way ANOVA, and Levene’s test.

Early cartilage damage
The Professional LxH Dynamic Disc Model can be used to show early cartilage damage.

What Were the Results?

According to the results, increased mechanical hypersensitivity paired with altered weight-bearing was shown by loaded mice. The initial ipsilateral cartilage lesions (that were at the one-week post-loading point) grew worse at the three and six-week points. The observed increase in lesion severity correlated with the development of mechanical hypersensitivity.

Furthermore, loaded mice also showed increased synovitis when compared to the control mice at the one-week post-loading points. However, the said increase returned to normal during the third and sixth week. Also, cortisol levels increased only during the one-week post-loading timeline.

Take note; there was no change in the subchondral bone integrity and nerve volume.

What was Concluded?

The study indicated that even though initial stress reaction, as well as local inflammation, was induced by loading, the said processes aren’t directly deemed responsible for the observed nociceptive phenotype.

However, allodynia induced by MJL is mainly associated with the cartilage lesions’ OA-like progression.

The team also noted that more still needs to be done to improve the understanding of how nociceptive behavior is induced by cartilage damage as well as which types of tissue pathologies could potentially play a role in pain associated with OA.

The current study’s team hopes that their current research might help others analyzing the MJL model’s pain-structure relationship.