How does synovial fluid work?
Synovial fluid is the dialysate of plasma and hyaluronan-rich ultrafiltrate that lubricates and nourishes diarthrodial joints; research into its markers, its inflammatory mediators and its response to intra-articular pre
Synovial fluid is the viscous, non-Newtonian ultrafiltrate of plasma that occupies the cavity of diarthrodial (synovial) joints, tendon sheaths and bursae. It is also called synovia. It is not a single chemical entity but a biological fluid: a plasma dialysate whose defining macromolecular component is hyaluronic acid (HA), a high-molecular-weight glycosaminoglycan of repeating disaccharide units of D-glucuronic acid and N-acetyl-D-glucosamine. Because it is a fluid rather than a compound, no sequence, formula or molecular weight applies to synovial fluid as a whole; those identifiers apply to its constituents, such as HA, and to the protein markers measured within it.
The pathway most often interrogated in the studies below is the inflammatory cytokine axis — tumour necrosis factor alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) — together with the NLRP3 inflammasome and its adaptor TXNIP, which regulate inducible nitric oxide synthase (iNOS) and downstream cartilage degradation.
Research Studies
Hyaluronic acid injection and TNF-alpha and IL-1 beta in knee osteoarthritis
A registered clinical study is determining the effect of intra-articular HA injection therapy on pre- and post-treatment TNF-alpha and IL-1 beta levels, and on methylation changes, in blood and synovial fluid of patients with knee osteoarthritis, compared with a placebo group. The same study evaluates the effects of HA injection on pain, functional status and quality of life, and relates those effects to changes in TNF-alpha and IL-1 beta [3].
REJENERA and the NLRP3-TXNIP-iNOS axis in a rat osteoarthritis model
REJENERA, a multi-component bioflavonoid-based formula, was tested for alleviation of osteoarthritis and chondroprotection by regulating the NLRP3-TXNIP-iNOS axis and inflammation. The formula contains primarily olive leaf bioflavonoids (ZeyEX, quercetin and luteolin), S-allylcysteine, palmitoylethanolamide, L-proline, hyaluronic acid and boron. In the study, knee osteoarthritis was established in rats by intra-articular injection of monosodium iodoacetate (MIA; 3 mg) into the right knee joint, and REJENERA was compared with ZeyEX, NPROC (collagen-rich eggshell membrane combined with olive leaf extract) and ibuprofen [1]. This is an animal-model finding.
Autologous bone marrow aspirate and combined lipoaspirate with leukocyte-poor PRP in knee osteoarthritis
The ABLE OA trial is a Health Canada authorised phase II/III, multi-centre, prospective, double-blinded, randomised, placebo-controlled adaptive trial evaluating two minimally manipulated autologous cellular preparations: bone marrow aspirate (BMA) injection, and combined lipoaspirate micronised (LAM) with leukocyte-poor platelet-rich plasma (LP-PRP) injections, for the treatment of knee osteoarthritis. BMA, LAM from lipoaspirate and LP-PRP from whole blood are prepared using the Cervos Marrow Cellution Bone Marrow Aspiration System, Cervos LIPO-PRO Adipose Transfer System and Cervos KEYPRP Platelet Separator System respectively [4].
Collagen peptide supplementation and connective tissue remodelling after total knee arthroplasty
A clinical study is examining the effects of collagen peptide supplementation on connective tissue remodelling, functional outcomes and wound healing after total knee arthroplasty (TKA). Recruitment is performed by checking the calendar for scheduled TKA procedures more than 8 weeks ahead in the UAMS orthopedic clinic, with clinic staff screening basic inclusion and exclusion criteria in the electronic medical record and either contacting patients directly or passing contact information to the principal investigator [2].
Serum and synovial markers in periprosthetic joint infection
Total joint replacement is an increasingly effective orthopedic procedure, but failure due to aseptic or septic loosening remains an important problem, often driven by patient predisposing factors that determine the need for revision surgery. Against the still-open questions about the diagnostic accuracy of serum and synovial fluid markers in periprosthetic joint infection (PJI), a diagnostic clinical study in patients hospitalised for revision is evaluating the diagnostic accuracy and cost-effectiveness of combining serum and/or synovial markers [6].
Alpha-defensin and synovial proteins in paediatric septic arthritis
Differentiating septic arthritis from other causes of joint inflammation in paediatric patients is challenging and important, because septic arthritis requires surgical debridement as part of treatment. The current gold standard for diagnosis in children is a positive synovial fluid culture, but joint cultures may take several days to return, and surgeons frequently must decide whether to debride a joint before culture results are available. No single laboratory test or clinical feature reliably makes that distinction [8].
Acthar and synovial inflammation in rheumatoid arthritis
In a study of synovial inflammation in rheumatoid arthritis, patients are assigned to receive either Depo Medrol or Acthar treatment. A synovial biopsy, blood draws, synovial fluid aspiration and physician assessments are performed before and after initiating treatment [7].
Borrelia B-cell diagnostics and synovial-adjacent immune sampling
The BRILLIANT study is a single-centre, prospective observational study in children with Lyme disease, assessing the immune response against Borrelia burgdorferi. One objective is development of a Bb-specific ASC ELISpot as a new test method for diagnosis of early Lyme disease, addressing the low sensitivity of current standard two-tier testing in recently infected patients and the false positives that can arise in recovered patients from long-term persistence of antibodies against Bb [5].
Comparison of study designs and sample matrices
| Study | Preparation or intervention | Model or population | Matrix analysed |
|---|---|---|---|
| REJENERA comparative study [1] | REJENERA vs ZeyEX vs NPROC vs ibuprofen | Rat, MIA-induced knee OA | Joint tissue (NLRP3-TXNIP-iNOS axis) |
| HA injection study [3] | Intra-articular HA vs placebo | Human knee OA | Blood and synovial fluid |
| ABLE OA [4] | BMA vs saline; LAM + LP-PRP vs saline | Human knee OA | Autologous cellular preparations |
| PJI marker study [6] | Combined serum and/or synovial markers | Patients hospitalised for revision | Serum and synovial fluid |
| Paediatric septic arthritis study [8] | Alpha-defensin and synovial proteins | Paediatric patients | Synovial fluid |
If you are reading this for personal health reasons
The materials described here are supplied for laboratory research use only, and we do not provide dosing, diagnostic or medical guidance of any kind. Nothing on this page is a recommendation for use in a person. Anyone considering a compound or procedure for themselves should speak to a licensed clinician.
Sources
- [1] REJENERA, a multi-component bioflavonoid-based formula, alleviates osteoarthritis and provides chondroprotection by regulating the NLRP3-TXNIP-iNOS axis and inflammation: a comparative study with olive leaf nutraceuticals and ibuprofen
- [2] Effects of Collagen Peptide Supplementation on Connective Tissue Remodeling, Functional Outcomes, and Wound Healing After Total Knee Arthroplasty (TKA)
- [3] The Effect of Hyaluronic Acid Injection on TNF-Alpha and IL-1β in Knee Osteoarthritis
- [4] Autologous BMA vs Saline and LAM + LP-PRP vs Saline Evaluations in Knee OA
- [5] Borrelia B-cell Diagnostics
- [6] Periprosthetic Joint Infections: Diagnostic Accuracy and Cost-effectiveness Analysis of Serum and Synovial Markers
- [7] The Effects of Acthar on Synovial Inflammation in Rheumatoid Arthritis
- [8] Alpha-Defensin and Synovial Proteins to Improve Detection of Pediatric Septic Arthritis