Basic Science Tip #523

PRP and cytokines in osteoarthritis: Are there evil humors?

Platelet rich plasma has been used to treat a wide variety of clinical conditions including recent injury, tendonopathy, and osteoarthritis. However, there is a gap between understanding the science of what is injected and how an individual responds to their PRP preparation. These variables include cytokine levels, preparation method, inclusion of lymphocytes, and demographics (1).

The authors highlighted the effects of age on platelet rich plasma used in osteoarthritis. In clinical practice PRP used for knee osteoarthritis is usually from older individuals. The authors hypothesized that lower levels of the inflammatory mediators interleukin-1β, and tumor necrosis factor α (TNF-α) and that higher levels of the growth factors (GFs), insulin-like growth factor 1, and transforming growth factor β1 within leukocyte-poor PRP would correlate with more favorable chondrocyte and macrophage responses in vitro. They compared 10 healthy males aged 23-33 and 10 knee osteoarthritis patients aged 62-85. Enzyme-linked immunosorbent assays were used to evaluate cytokine expression of 10% PRP and three-dimensional alginate bead chondrocyte cultures and monocyte-derived macrophage cultures were treated with 10% PRP from all 20 donors. For chondrocyte culture plain chondrocyte media was used as a negative control and TGF-β enchanced media as a positive control. Plain macrophage media was the negative control for macrophages and lipopolysaccharide was the positive control.

Platelet concentration was less in the OA group. Insulin like growth factor and transforming growth factor β were increased in the PRP from normals versus the OA patients. TNF-α and metalloprotease 9 (a degradative endopeptidase) was greater in the PRP from the older OA patients. mRNA expression for Col1a1, Col2a1, Sox9 were all significantly greater in the young PRP preparation s in contrast to OA PRP. Except for Col1a1 the negative control matched the young PRP. MMP1, 3, 9, 13 were all significantly greater for the young PRP than the OA PRP and both were greater than the negative control. TNF-α was not significantly elevated over control in the young PRP group but was greater of the OA PRP. The pattern was the same for MMP9 with a slight elevation over control for the young PRP.

Over all, it appeared that PRP from older individuals with OA contain unknown factors that may suppress chondrocyte matrix synthesis and promote macrophage inflammation in vitro.

The American Academy of Orthopaedic Surgeons is now taking the lead in a “strategic investment in the field of biologics.” AAOS president, Kristy Weber, goes on the state that as the world’s largest medical association of musculoskeletal specialists the academy has a responsibility to advance the quality of orthopaedic care in a fully transparent and scientific way. At present patients, surgeons and other healthcare specialists are navigating the field independently without reliable sources of information. Now is the time for AAOS to lead the way!

Reference

1. O'Donnell C, Migliore E, Grandi FC, Koltsov J, Lingampalli N, Cisar C, Indelli PF, Sebastiano V, Robinson WH, Bhutani N, Chu CR. Platelet-Rich Plasma (PRP) From Older Males With Knee Osteoarthritis Depresses Chondrocyte Metabolism and Upregulates Inflammation. J Orthop Res. 2019 May 1. doi: 10.1002/jor.24322. [Epub ahead of print] PMID: 31042308