Clinically Relevant Molecular Biomarkers for Use in Human Knee Osteoarthritis: A Systematic Review

Convill, James; Tawy, Gwenllian; Freemont, Anthony J.; Biant, Leela

doi:10.1177/1947603520941239

Cited by 21 publications

(19 citation statements)

References 81 publications

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“…Despite a huge ongoing effort in the detection of blood-based diagnostic markers, no single blood biomarker has emerged so far, however. 6 Previous studies have suggested a potential role of fatty acid–binding protein 4 (FABP4), oxidized low-density lipoprotein (oxLDL), membrane-bound phospholipase A2 (PLA2G2A) and soluble receptor for advanced glycation end-products (sRAGE) in the pathogenesis of osteoarthritis (OA). 7-10 Cytoplasmic FABP4, a member of the FABP superfamily and mostly expressed in adipocytes, regulates intracellular fatty acid transportation by increasing fatty acid solubility and facilitating transport to cellular compartments and specific enzymes.…”

Section: Introductionmentioning

confidence: 99%

Fatty Acid–Binding Protein 4 (FABP4) Is Associated with Cartilage Thickness in End-Stage Knee Osteoarthritis

et al. 2021

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Background There is no single blood biomarker for the staging of knee osteoarthritis (KOA). The purpose of this study was to assess the relationship of obesity, serum biomarkers, the hip-knee-ankle angle (HKAA) with sonographic cartilage thickness. Methods We conducted a cross-sectional study of n = 33 patients undergoing knee arthroplasty. Body mass index (BMI) was recorded, and patients were grouped based on BMI. Serum blood samples were collected, and the following biomarkers were measured using the ELISA technique (subgroup of n = 23): oxidized low-density lipoprotein (oxLDL), soluble receptor for advanced glycation end-products (sRAGE), fatty acid–binding protein 4 (FABP4), membrane-bound phospholipase A2 (PLA2G2A). The HKAA was analyzed on full-length limb standing x-ray images. Cartilage thickness was assessed on ultrasound images. Multivariable regression analysis was performed to account for confounding. Results After adjusting for age, gender, and HKAA, obese patients had thicker medial femoral cartilage (β = 0.165, P = 0.041). Furthermore, lateral cartilage thickness was negatively correlated with FABP4 level after adjusting for of age, gender, BMI, and HKAA (β = −0.006, P = 0.001). Confirming previous studies, after adjustment, FABP4 level was associated with a higher BMI group (β = 42.99, P < 0.001). None of the other markers (oxLDL, PLA2G2A, and sRAGE) was associated with BMI or cartilage thickness. Discussion Our results indicate that BMI has a weak, positive association with cartilage thickness in end-stage KOA patients. FABP4 levels were negatively associated with cartilage thickness. While our study is limited by a small sample size, these results further highlight the role of FABP4 as promising biomarkers of burden of disease in KOA.

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Section: Introductionmentioning

confidence: 99%

Fatty Acid–Binding Protein 4 (FABP4) Is Associated with Cartilage Thickness in End-Stage Knee Osteoarthritis

et al. 2021

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“…Furthermore, bone and cartilage metabolism biomarkers such as Vitamin D, CTX-II, PINP [ 31 ], MMP3, and COMP [ 32 ], along with lipid markers such as adiponectin [ 33 ], leptin [ 34 ], resistin, and visfatin [ 35 ], were analyzed in both groups. Among all the biomarkers studied, there was a significant increase in the MMP3 level and decreased vitamin D levels in OA rats compared to the sham group at 12 weeks postOA.…”

Section: Resultsmentioning

confidence: 99%

“…In addition, the lack of a significant difference between the OA and sham-OP rats, regarding the transforming growth factor-beta 1 (TGf-β1) and C-reactive protein levels, indicated that our OA induction on the single joint did not involve systemic inflammation. Furthermore, bone and cartilage metabolism biomarkers such as Vitamin D, CTX-II, PINP [31], MMP3, and COMP [32], along with lipid markers such as adiponectin [33], leptin [34], resistin, and visfatin [35], were analyzed in both groups. Among all the biomarkers studied, there was a significant increase in the MMP3 level and decreased vitamin D levels in OA rats compared to the sham group at 12 weeks postOA.…”

Section: Serum Level Oa Biomarkers' Detection and Evaluationmentioning

confidence: 99%

Detection and Evaluation of Serological Biomarkers to Predict Osteoarthritis in Anterior Cruciate Ligament Transection Combined Medial Meniscectomy Rat Model

Huang

Yang

Busa

et al. 2021

IJMS

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Biomarkers are essential tools in osteoarthritis (OA) research, clinical trials, and drug development. Detecting and evaluating biomarkers in OA research can open new avenues for researching and developing new therapeutics. In the present report, we have explored the serological detection of various osteoarthritis-related biomarkers in the preclinical model of OA. In this surgical OA model, we disrupted the medial tibial cartilage’s integrity via anterior cruciate ligament transection combined with medial meniscectomy (ACLT+MMx) of a single joint of Wistar rats. The progression of OA was verified, as shown by the microscopic deterioration of cartilage and the increasing cartilage degeneration scoring from 4 to 12 weeks postsurgery. The concentration of serological biomarkers was measured at two timepoints, along with the complete blood count and bone electrolytes, with biochemical analysis further conducted. The panel evaluated inflammatory biomarkers, bone/cartilage biomarkers, and lipid metabolic pathway biomarkers. In chronic OA rats, we found a significant reduction of total vitamin D3 and C-telopeptide fragments of type II (CTX-II) levels in the serum as compared to sham-operated rats. In contrast, the serological levels of adiponectin, leptin, and matrix metallopeptidase (MMP3) were significantly enhanced in chronic OA rats. The inflammatory markers, blood cell composition, and biochemical profile remained unchanged after surgery. In conclusion, we found that a preclinical model of single-joint OA with significant deterioration of the cartilage can lead to serological changes to the cartilage and metabolic-related biomarkers without alteration of the systemic blood and biochemical profile. Thus, this biomarker profile provides a new tool for diagnostic/therapeutic assessment in OA scientific research.

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“…As the most widely studied and applied biomarker in clinical practice, calprotectin is known to be a promising noninvasive biomarker of inflammatory bowel disease (IBD). 16-18 Fecal calprotectin is reported to be strongly associated with disease activity indices and endoscopic activity in IBD. 16 Recently, serum calprotectin has also attracted attention as a novel blood-based biomarker of IBD, which correlates with endoscopic findings of the patients.…”

Section: Discussionmentioning

confidence: 99%

Serum Calprotectin as a Blood-Based Biomarker for Monitoring Knee Osteoarthritis at Early but Not Late Stages

et al. 2020

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Objective The identification of early-stage osteoarthritis (OA) is crucial for the deceleration of its progression; however, no reliable biomarker is available for this purpose. The current study aimed to determine the role of serum calprotectin in the detection of early-stage knee OA. Design In a case-control study, serum samples were collected from 84 patients with primary bilateral knee OA and 52 healthy controls. The radiographic grading of knee OA was performed using the Kellgren-Lawrence classification system. Serum concentrations of calprotectin were measured using an enzyme-linked immunosorbent assay. Results The mean serum calprotectin level was 2908 ± 2516 ng/mL in OA patients and 901 ± 875 ng/mL in healthy control subjects ( P < 0.001). Mean serum calprotectin levels were significantly higher in the lower stages of OA: 3740 ± 2728 ng/mL in OA grade I, 3100 ± 2084 ng/mL in OA grade II, 2246 ± 1418 ng/mL in OA grade III, and 2035 ± 765 ng/mL in OA grade IV ( P = 0.047). Serum calprotectin levels were significantly higher in patients with a disease duration <42 months compared with those with a disease duration >42 months ( P = 0.043). Conclusion Serum calprotectin level increases significantly in the early stages of OA and shows a reverse association with disease severity. Therefore, it could be suggested as a promising blood-based marker for early-stage knee OA.

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Clinically Relevant Molecular Biomarkers for Use in Human Knee Osteoarthritis: A Systematic Review

Cited by 21 publications

References 81 publications

Fatty Acid–Binding Protein 4 (FABP4) Is Associated with Cartilage Thickness in End-Stage Knee Osteoarthritis

Fatty Acid–Binding Protein 4 (FABP4) Is Associated with Cartilage Thickness in End-Stage Knee Osteoarthritis

Detection and Evaluation of Serological Biomarkers to Predict Osteoarthritis in Anterior Cruciate Ligament Transection Combined Medial Meniscectomy Rat Model

Serum Calprotectin as a Blood-Based Biomarker for Monitoring Knee Osteoarthritis at Early but Not Late Stages

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