Wnt signaling as a translational target in rheumatoid and psoriatic arthritis

Abstract

Background

Rheumatoid arthritis (RA) and Psoriatic arthritis (PsA) are chronic inflammatory diseases mainly affecting joints. RA primarily targets the synovial joints and is characterized by cartilage and bone erosion, whereas PsA is associated with skin and nail psoriasis and is characterized by erosive bone damage with an exuberant bone formation and soft tissue involvement. Recent evidence described the involvement of the Wnt pathway in the pathogenesis of these diseases. Thus, we aimed to analyze some components of Wnt signaling, i.e. DKK1, Wnt 5a and β-catenin, and their association with disease activity indices, investigating possible differences between the two diseases.

Methods

Sera from 18 RA patients naïve for biological therapy, 18 PsA patients and 20 matched healthy donors (HD) were tested for DKK1 by ELISA, Wnt 5a and β-catenin by Immunoblotting. Values were correlated with CTX-1, detected by ELISA, and with disease activity indices: Disease Activity Score on 28 joints (DAS28-CRP) for RA and the Disease Activity in Psoriatic Arthritis (DAPSA) score for PsA.

Results

This study highlights significant increase in DKK1, Wnt 5a, and β-catenin levels in RA and PsA patients compared to HD, with distinct patterns of correlation with disease activity indices. Indeed, in RA patients, DKK1 levels positively correlated with DAS28-CRP score, whereas in PsA patients, DKK1 levels negatively correlated with DAPSA score. Our findings showed a strong correlation between DKK1 and CTX-1 levels in RA patients, supporting the relationship between DKK1 levels and the presence of joint erosions. Furthermore, a significant positive correlation was found between β-catenin and IL-6 levels in RA, indicating that β-catenin may be involved in the inflammatory cascade.

Conclusion

This study compares the involvement of Wnt signaling in RA and PsA, suggesting that Wnt signaling may represent a possible mechanism of disease activity. In particular, it indicates that DKK1 levels are correlated with CTX-1, a marker of bone resorption, and with disease activity in RA patients. These findings underscore the importance of these biomarkers in the potential monitoring of patients, offering insights into disease mechanisms and potential therapeutic targets.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12967-025-06174-2.

Background

Rheumatoid arthritis (RA) and Psoriatic arthritis (PsA) are chronic inflammatory diseases mainly affecting joints. Despite differences in pathogenesis clinical presentation, radiographic findings, comorbidities, both conditions may lead to significant disabilities impacting the quality of life [1, 2]. RA is an autoimmune disease that primarily targets the synovial joints and is characterized by cartilage and bone erosion [3–4]. Differently, PsA is associated with skin and nail psoriasis and is characterized by erosive bone damage associated with an exuberant bone formation, often associated with soft tissue involvement (i.e. enthesitis and dactylitis) [5]. Both RA and PsA have a multifactorial etiology [1, 5, 6]. The recent characterization of the canonical Wnt pathway in the regulation of bone modeling and remodeling provided important insights in understanding the pathophysiology of both RA and PsA. Indeed, different studies described the involvement of the Wnt pathway in the pathogenesis of these diseases [7, 8]. Notably, the Wnt/β-catenin signaling regulates osteoblast proliferation, maturation and differentiation and, along with bone morphogenetic proteins, acts as the master regulator of osteogenesis [5–10] Wnt family in humans currently includes almost 19 different glycoproteins that can trigger multiple signaling cascades: the “canonical pathway”, also known as the “Wnt /β-catenin pathway”, initiated by Wnt 1, Wnt 3a, Wnt 5a, Wnt 7, Wnt 8a, Wnt 8b, Wnt 9a, and several “noncanonical pathways”, initiated by Wnt1, Wnt 3a, Wnt 4, Wnt 5, Wnt 11 and Wnt 16 [7, 11]. Wnt ligands bind their 7-pass transmembrane Frizzled receptors and the co-receptor low-density lipoprotein receptor-related protein (LRP) 5/6 to trigger the canonical pathway. This process leads β-catenin to accumulate in the cytoplasm and then translocate into the nucleus, where it binds members of the T cell factor/lymphoid enhancer factor (TCF/LEF) family to regulate the expression of the target gene of Wnt signaling pathway. However, Wnt family is involved in multiple cellular activities crucial for cellular function and non-canonical pathways, playing a crucial role in cytoskeletal reorganization and chondrocyte stacking [7, 12–14]. Dickkopf-1 (DKK1), an inhibitory molecule that regulates the Wnt pathway, has been recently recognized as a key player in animal models of arthritis and joint damage [8, 15].

Increased DKK1 levels are linked to bone resorption [16], whereas decreased levels are linked to new bone formation [17]. In this concern, a well-known marker of bone resorption is represented by C-terminal telopeptide of type 1 collagen (CTX-1), which has been demonstrated to be elevated in serum of RA patients [18, 19]. A recent study on a mouse model of RA showed that by inhibiting DKK1, the bone-destructive pattern of typical RA was reversed to the bone-forming pattern of osteoarthritis [8]. Indeed, some studies showed a correlation between the increased circulating DKK1 and structural severity, radiological progression, and bone erosion in recent-onset RA [20].

Moreover, different studies showed that serum level of DKK1 is elevated in patients with RA compared to healthy controls, suggesting a role for DKK-1 in the pathogenesis of RA [21, 22]. Instead, data on DKK1 in PsA are more controversial [23], with some studies showing higher serum levels in patients compared to healthy subjects and a statistically significant association between serum DKK1 levels and the presence of joint erosions detected by ultrasound examinations [24–28]. Other studies reported lower levels of DKK1 in PsA patients compared to both RA patients and the healthy controls [23, 29]. Similarly to DKK1, Wnt 5a and β-catenin could also play a role in the pathogenesis of both RA and PsA [30–32]. Elevated levels of circulating Wnt 5a, which activates the non-canonical Wnt pathway, may be a potential biomarker for identifying patients with RA associated with pulmonary complications [32]. An increased concentration of Wnt 5a was detected in the synovium of patients with RA and an inhibition of Wnt 5a reduced the proliferation of fibroblast-like synoviocytes (FLS) derived from both RA patients and animal models [33, 34]. Emerging evidence supports the involvement of the Wnt 5a-activated signaling cascades in the development of PsA and some studies revealed higher expression of Wnt 5a mRNA and protein in CD14 + monocyte-derived osteoclasts from PsA patients than in those from healthy controls [35–37]. The increased expression of Wnt 5a in the osteoclasts of damaged joints confirms its pathogenic role in active osteoclastogenesis in PsA patients [35]. Moreover, the activation of Wnt signaling pathway can lead to an increase in β-catenin levels in RA FLS [38, 39], contributing to their activation. Interestingly, observations confirmed the increase of β-catenin levels in the cartilage of animal models of PsA [40].

Since Wnt signaling might be considered a possible mechanism triggering bone damage, we undertook a study to evaluate the involvement of Wnt signaling in patients with RA and PsA with the purpose to underline its relationship with disease activity. Thus, given the conflicting results of the studies published in recent years [22, 23, 28], we aimed to analyze some components of Wnt signaling, i.e. DKK1, Wnt 5a and β-catenin, in both RA and PsA and their association with disease activity indices, investigating possible differences between the two diseases.

Methods

Patients

We enrolled 18 RA patients (17 females; 1 male) and PsA (7 females; 11 males) followed-up at Rheumatology Unit of Sapienza University of Rome. Patients with a diagnosis of RA, without extra-articular manifestations or comorbidities, naïve for biological therapy, were classified according to the American College of Rheumatology/European League Against Rheumatism 2010 criteria [41] and patients with PsA according to the Classification criteria for Psoriatic Arthritis (CASPAR) criteria [42]. Demographic (sex, age), clinical (disease duration, number of tender and swollen joints, disease activity indices, ongoing treatment), serological data [rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (ACPA) positivity], were collected. Sera from 20 age- and sex-matched HD were used as control group. Sera were collected on the day of the visit and stored at − 20° C until use. This study was conducted in compliance with the Helsinki Declaration, approved by local ethical Committee of Sapienza University of Rome (Protocol number 109/18), and participants gave written informed consent.

Detection of DKK1 by ELISA

DKK1 levels in serum samples from RA, PsA and HD were quantified using an Abcam ELISA kit [23, 27]. Serum samples were collected, processed and analyzed according to the manufacturer’s instructions. Microplate wells were coated with anti-DKK1 antibody overnight, blocked with buffer, and incubated with diluted samples (1:2) and standards. After incubation, wells were washed, and biotinylated detection antibody and streptavidin-HRP conjugate were added successively. Color development was achieved with TMB substrate and absorbance was measured at 450 nm. DKK1 concentrations were determined using a standard curve.

Detection of Wnt 5a and β-catenin by immunoblotting

Sera (3 μl) obtained from each subject with RA, PsA or HD were diluted with 72 μl radioimmunoprecipitation assay (RIPA) buffer and heated at 95° C for 2 min in sodium dodecyl sulfate-(SDS) loading buffer [43]. Samples were separated by SDS-PAGE using 10% polyacrylamide gels. Proteins were transferred onto PVDF membranes using a wet transfer system. Membranes were blocked with 5% albumin in TBST and incubated overnight at 4 °C with primary antibodies against Wnt 5a (1:1000 dilution, Cell Signaling Technology) and β-catenin (1:1000 dilution, Abcam). After washing, membranes were incubated with HRP-conjugated secondary antibodies for 1 h at room temperature. Protein bands were visualized using enhanced chemiluminescence (ECL) substrate. Densitometric analysis was performed using the ImageJ software (National Institutes of Health, Bethesda, MD, USA). Band intensities were normalized using serum albumin as loading control.

Detection of CTX-1 by ELISA

Serum levels of CTX-1 were quantified by ELISA kit by Novus Biologicals. Microplate precoated with CTX-1 antibodies were incubated with serum of RA, PsA patients and HD (1:2). After incubation, wells were washed, and biotinylated detection antibody and streptavidin-HRP conjugate were added successively. Color development was achieved with TMB substrate and absorbance was measured at 450 nm. CTX-1 concentrations were determined, using a standard curve.

Clinical correlation

The concentrations of DKK1, Wnt 5a and β-catenin were then correlated with disease activity indices: Disease Activity Score on 28 joints (DAS28-CRP) using C-reactive protein (CRP-based) for RA, or the Disease Activity in Psoriatic Arthritis (DAPSA) score for PsA.

Detection of proinflammatory interleukin-6

Interleukin-6 (IL-6) and Tumor Necrosis Factor α (TNF-α) were evaluated using OptEIA kits (BD Biosciences), following the manufacturer’s instructions.

Statistical analysis

All the statistical analyses were performed by GraphPad Prism software Inc. (San Diego, CA, USA). D’Agostino-Pearson omnibus normality test was used to assess the normal distribution of the data. Correlation analysis was carried out by Spearman test. Significance levels were denoted by asterisks: * p < 0.05, ** p < 0.005, *** p < 0.001, and **** p < 0.0001.

Results

Demographic, clinical and serological characteristics of patients

We enrolled 18 patients with RA and 18 with PsA. Demographic and clinical data are summarized in Table 1.

Table 1.

Demographic, clinical and serological characteristics of patients

	RA (n = 18)	PsA (n = 18)
F: M	17:1	7:11
Age, mean (SD)	56.5 (10.7)	54.1 (10.9)
Disease duration, years	11.5 (11.1)	11.7 (7.86)
DAS28-CRP, mean (SD)	3.5 (1.4)	na
DAPSA, mean (SD)	na	13.0 (9.9)
Axial involvement	na	6 (33.3)
RF, n (%)	13 (72.2)	0
aCCP	13 (72.2)	0
No treatment, n (%)	5 (27.8)	6 (33.3)

DAS28-CRP: disease activity score on 28 joints_C-Reactive Protein; DAPSA: Disease Activity Index in Psoriatic Arthritis; PsA: Psoriatic arthritis, RF: Rheumatoid Factor; CCP, anti-cyclic citrullinated protein

Evaluation of DKK1 levels in RA and PsA patients

We detected significantly higher levels of DKK1 in the sera of RA patients compared to both HD (p < 0.0001) and PsA patients (p < 0.001) (Fig. 1A). These findings suggest a strong association between elevated DKK1 levels and RA. Elevated DKK1 levels in RA might be indicative of a more pronounced osteoclastogenesis and subsequent bone erosion, a hallmark of the disease [8, 28] Additionally, PsA patients also exhibited significantly higher DKK1 levels compared to HD (p < 0.0001). In these patients DKK1 elevation may be related more to enthesitis and new bone formation.

Fig. 1.

Evaluation of DKK1, Wnt 5 A, β-catenin levels in RA and PsA patients. A DKK1 levels in serum samples from healthy donors HD (n = 20), patients with RA (n = 18), and patients with PsA (n = 18) were quantified using an ELISA kit. B Wnt 5a and C β-catenin levels were detected by Western blot in the sera of HD, RA or PsA patients. Values of the 3 patients without joint erosions in RX are indicated in red. Densitometric values of Wnt 5a or β-catenin levels are represented and summarized by Scatter plot analysis. Each assay (ELISA, WB) was performed in triplicate. ** p < 0.005, *** p < 0.001, and **** p < 0.0001

Assessment of Wnt 5a levels in RA and PsA patients

In the same patients, Wnt 5a levels were analyzed, showing a similar trend to DKK1. In fact, both RA and PsA patients exhibited significantly higher Wnt 5a levels compared to HD (p < 0.0001 for both comparisons) (Fig. 1B, Figure S1). Levels of Wnt 5a were significantly higher in RA than in PsA patients (p < 0.005).

These results indicate that Wnt 5a is markedly elevated in both RA and PsA, pointing to its potential role in the pathogenesis of both conditions. The elevation of Wnt 5a in both types of arthritis suggests its involvement in inflammatory processes and possibly in joint remodeling [30, 37].

Evaluation of β-catenin levels in RA and PsA patients

We also found higher β-catenin levels in both RA and PsA patients compared to HD (p < 0.0001 for both comparisons) (Fig. 1C, Figure S1). However, no significant difference was observed between RA and PsA patients. This suggests that elevated β-catenin levels are a common feature in both types of arthritis, potentially contributing to their inflammatory processes [38–40].

Correlation with disease activity indices

The values obtained for DKK1, Wnt 5a and β-catenin were correlated with key indices of disease activity.

We observed that in RA patients, DKK1 levels positively correlated with the DAS28-CRP score (p = 0.0216, r = 0.5369) (Fig. 2A), indicating that higher DKK1 levels are associated with higher disease activity. No significant correlation was found between DKK1 levels and disease duration in RA. Interestingly, the lowest levels of DKK1 were observed in the 3 patients without joint erosions in RX (mean value 14188 pg/ml vs. 24564, p = 0.003) (Fig. 2A, red). Elevated DKK1 levels in RA patients may reflect heightened osteoclast activity and inflammatory processes, contributing to more severe disease manifestations [28]. Thus, we evaluated DKK1 correlation with the CTX-1 levels, a reliable marker for bone erosion in RA, which was shown to be appropriate to investigate the relation between inflammation and bone and cartilage destruction [44, 45]. The comparative analysis revealed that in RA patients DKK1 positively correlated with the CTX-1 levels (p = 0.0062, r = 0.6185, Fig. 2C). Again, the 3 patients without joint erosions in RX showed low levels of CTX-1 (mean value 0.7 ng/ml vs. 1.5 ng/ml, p < 0.05) (Fig. 2C, red).

Fig. 2.

Correlation of DKK1 with disease activity indices, CTX-1 and sex/age. A Correlation between DKK1 levels and DAS28-CRP score in RA patients. Values of the 3 patients without joint erosions in RX are indicated in red. B Correlation between DKK1 levels and DAPSA score in PsA patients. C Correlation between DKK1 levels and CTX-1 in RA patients. Values of the 3 patients without joint erosions in RX are indicated in red. D Correlation between DKK1 levels and CTX-1 in PsA patients. Correlation analysis was carried out by Spearman test. E DKK1 levels in premenopausal women, postmenopausal women and men. Results show a significant difference of postmenopausal women vs. premenopausal women. *p < 0.05. F CTX-1 levels in premenopausal women, postmenopausal women and men. Results show a significant difference of postmenopausal women and men vs. premenopausal women. *p < 0.05

On the contrary, in PsA patients, DKK1 levels were negatively correlated with the DAPSA score (p = 0.0509, r = -0.4667) (Fig. 2B), suggesting that lower DKK1 levels are associated with higher disease activity. This inverse relationship contrasts with the positive correlation observed in RA, highlighting potential differences in the role of DKK1 between these diseases. Additionally, DKK1 levels showed a positive correlation with PsA disease duration (p = 0.017, r = 0.6), suggesting that DKK1 levels increase over the course of the disease. No significant correlation was shown between DKK1 and CTX-1 levels (p = 0.1168, r = 0.3829, Fig. 2D).

When the data were analyzed by disaggregating it by sex and age, the results revealed a significant increase in DKK1 (Fig. 2E) and CTX1 levels in men and post-menopausal women compared to pre-menopausal women (p < 0.05) (Fig. 2F).

As showed in Fig. 3A, no significant correlation emerged between Wnt 5a levels and the disease activity in RA (Fig. 3A), whereas Wnt 5a levels negatively correlated with DAPSA (p = 0.0452, r = -0.4773) (Fig. 3B) in PsA patients, implying that higher Wnt 5a levels might be associated with lower disease activity in PsA. This inverse correlation could reflect a regulatory mechanism where Wnt 5a influences disease progression or represents a response to inflammation [30, 37].

Fig. 3.

Correlation of Wnt 5a with disease activity. A Correlation between Wnt 5a levels and DAS28-CRP score in RA patients. B Correlation between Wnt 5a levels and DAPSA score in PsA patients

No significant correlation emerged between β-catenin levels and activity scores in RA and PsA patients. This finding suggests that elevated β-catenin levels may be related to the inflammatory processes involved in both arthritis rather than directly to disease activity. In this concern, we analyzed levels of proinflammatory cytokines IL-6 (Fig. 4A) and TNF-α (Fig. 4D), which revealed significantly higher values in the sera of RA and PsA patients compared to HD (p < 0.0001 and p < 0.0001, respectively). Additionally, RA patients also exhibited significantly higher levels of TNF-α compared to PsA (p < 0.05). Interestingly, a significant positive correlation was found between β-catenin and IL-6 levels in RA (p = 0.0151; r = 0.5624, Fig. 4B), indicating that β-catenin may be involved in the inflammatory cascade mediated by IL-6, a key cytokine in RA pathogenesis. Elevated β-catenin could thus contribute to the perpetuation of inflammation through interactions with other pro-inflammatory cytokines [38–40]. No significant correlation was shown between β-catenin and IL-6 levels in PsA patients (Fig. 4C). No significant correlation was also shown between β-catenin and TNF-α levels in both RA (Fig. 4E) and PsA patients (Fig. 4F).

Fig. 4.

Detection of proinflammatory cytokines IL-6 and TNF-α. A IL-6 levels in serum samples from HD (n = 20), patients with RA (n = 18) and patients with PsA (n = 18) were quantified by an ELISA kit. B Correlation between β-catenin levels and IL-6 in RA patients. C Correlation between β-catenin levels and IL-6 in PsA patients. D TNFα levels in serum samples from HD (n = 20), patients with RA (n = 18) and patients with PsA (n = 18) were quantified by an ELISA kit. E Correlation between β-catenin levels and TNF-α in RA patients. F Correlation between β-catenin levels and TNF-α in PsA patients

Correlation analyses were carried out by Spearman test. Levels are represented and summarized by Scatter plot analysis. * p < 0.05, **** p < 0.0001

Discussion

This study highlights significant increase in DKK1, Wnt 5a, and β-catenin levels in RA and PsA patients compared to HD, with distinct patterns of correlation with disease activity indices. Indeed, in RA patients, DKK1 levels positively correlated with DAS28-CRP score, indicating that higher levels are associated with higher disease activity, whereas in PsA patients, DKK1 levels negatively correlated with DAPSA score, suggesting that lower levels are associated with higher disease activity. In this study, the increased levels of DKK1 found in the serum of RA patients, compared to those with PsA and healthy individuals, may be linked to joint and bone remodeling. This is consistent with previous studies showing that DKK1 is associated with bone erosion in animal models of RA [8, 28, 46]. Although PsA and RA exhibit similarities in bone destruction, PsA is defined by new bone formation, and the destruction of cortical bone defines RA. Thus, the level of DKK1 was lower in patients with PsA than in those with RA, as also reported by Wang [47] and Diarra, et al. [8]. Our findings are also substantially in agreement with Fassio et al., who demonstrated that DKK1 levels were significantly higher in RA as compared to PsA patients [28] and were associated with both a lower bone mineral density (BMD) and the presence of typical erosions, suggesting that DKK1 overproduction may contribute to the locally increased bone resorption as well as impaired bone repair [48]. To verify this hypothesis, in the present study we evaluated whether in RA patients DKK1 levels correlated with CTX-1, a marker of bone resorption, since it reflects the degradation of type I collagen, a critical structural component of bone [18, 19]. Our findings showed a strong correlation between DKK1 and CTX-1 levels in these patients, supporting the relationship between DKK1 levels and the presence of joint erosions, which could be due to the role of DKK1 in promoting osteoclast activity and inhibiting bone formation. This finding is supported by the observation that CTX-1 has been related with bone erosion, as well as with disease activity in RA [18, 19].

Additionally, clinical studies have correlated higher serum DKK1 levels with increased disease activity and severity, further supporting its potential role as a biomarker for bone involvement in inflammatory arthritis [49, 50]. When the data were analyzed by disaggregating it by sex and age, our results showed a significant increase of DKK1 and CTX1 in men and post-menopausal women compared to pre-menopausal women. Although scientific literature demonstrates that increased serum levels of DKK1 in post-menopausal women correlate with reduced bone mass [51], the precise relationship between estrogens and DKK1 remains unclear. Studies in animal models indicated that silencing DKK1 in estrogen-deficient animals can improve bone health [52]. The decline in estrogen levels after menopause may also contribute to the negative effects observed on disease progression and severity in patients with RA [53].

Another finding of this work was that both RA and PsA patients exhibited significantly higher Wnt 5a levels than HD. Wnt 5a has been shown to be related to the inflammatory response in RA and PsA [35, 54–56]. In addition, Wnt 5a has been implicated in the regulation of synovial fibroblast activity, contributing to the pannus formation and joint destruction observed in RA [33]. The differential expression of Wnt 5a in RA compared to PsA may reflect distinct pathogenic mechanisms or disease phenotypes, with RA typically showing more aggressive synovial proliferation and bone erosion [28, 35].

Furthermore, the interaction between Wnt 5a and other signaling pathways, such as Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and c-Jun N-terminal kinase (JNK), highlights its role in modulating the inflammatory milieu [56]. The dual role of Wnt 5a in promoting inflammation and affecting bone remodeling underscores its significance in the complex pathophysiology of RA and PsA, warranting further investigation into its precise functions and therapeutic potential [30, 37].

We also found higher β-catenin levels in both RA and PsA patients compared to HD. Interestingly, a significant positive correlation was found between β-catenin and levels of the proinflammatory cytokine IL-6 in RA. β-catenin is a central component of the canonical Wnt signaling pathway, which is crucial in regulating cell proliferation, differentiation and survival [57]. In the context of inflammatory arthritis, β-catenin is involved in the activation and proliferation of synovial fibroblasts, which are key drivers of synovial hyperplasia and joint destruction. Studies have demonstrated that β-catenin can promote the expression of matrix metalloproteinases (MMPs) and other degradative enzymes, contributing to the breakdown of cartilage and bone [9, 57, 58]. Furthermore, β-catenin signaling regulates immune responses within the joint [59]. It can influence the behavior of various immune cells, including T cells and macrophages, thereby modulating the inflammatory environment. Elevated β-catenin levels in RA and PsA patients suggest that this pathway might be upregulated in response to chronic inflammation, leading to enhanced synovial fibroblast activation and subsequent joint damage. Inhibiting β-catenin could reduce synovial fibroblast proliferation, decrease the production of inflammatory mediators, and ultimately mitigate joint damage [38, 58, 59]. Overall, the elevation of β-catenin levels in both RA and PsA highlights its importance in the pathophysiology of these conditions. Further research is warranted to explore the therapeutic potential of modulating β-catenin signaling in inflammatory arthritis, to develop more effective treatments to prevent joint destruction and improve patient outcomes.

Probably, the main limitation of this study may be represented by the relatively small number of patients, which is justified by the high selection of patients. Further multicentric studies on larger cohorts of patients are needed to gain conclusive evidence.

As a whole, this study compares the involvement of Wnt signaling in RA and PsA, indicating that DKK1 levels are correlated with CTX-1, a marker of bone resorption, and with disease activity (DAS28-CRP score) in RA patients. These findings underscore the importance of these biomarkers in the potential monitoring of patients, offering insights into disease mechanisms and potential therapeutic targets. The differential expression and correlation patterns of these proteins in RA and PsA can inform future research directions, particularly in developing targeted therapies that address specific pathways involved in RA and PsA.

Conclusion

In conclusion, our study highlights involvement of Wnt signaling molecules in RA and PsA. This knowledge could open new perspectives, introducing new biomarkers that can be used for the clinical and prognostic monitoring of patients with RA and PsA.

Electronic supplementary material

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Abbreviations

ACPA

Anti-citrullinated protein antibodies

BMD

Bone mass density

CRP

C-reactive protein

CTX1

C-terminal telopeptide of type 1 collagen

DAPSA

Disease activity in Psoriatic arthritis

DAS28

Disease activity score 28

DKK1

Dickkopf-1

FLS

Fibroblast-like synoviocytes

HD

Heathy donors

IL-6

Interleukin-6

LRP

Low-density lipoprotein receptor-related protein

PsA

Psoriatic arthritis

RA

Rheumatoid arthritis

RF

Rheumatoid Factor

TCF/LEF

T cell factor/lymphoid enhancer factor

WNT

Wingless family signaling

Author contributions

M.S, G.R., F.S., C.A. and A.L. conceived and designed the work. G.R., D.C., C.G., V. M., A.C. and F.S. conducted the experiments and gathered the data. G.R., F.S., and V.M. analyzed and interpreted the data. G.R., D.C., A.C., V.M. drafted the manuscript. M.S., C.A., T.G., R.M., A.L., F.C. provided critical revisions and intellectual input to the manuscript. All authors read and approved the final version of the manuscript.

Funding

This research does not receive external funding.

Data availability

The original data applied in this research are accessible from the corresponding author. Data will made available on reasonable request.

Declarations

Ethics approval and consent to participate

This study was conducted in compliance with the Helsinki Declaration (2000). All participants were fully informed about the study requirements and were required to accept the data sharing and the privacy policy before participating in the study. All participants gave written informed consent. Our study was approved by the local Ethics Committee of Sapienza University of Rome (Protocol number 109/18).

Consent for publication

Not applicable.

Competing interests

All authors declared that there are no conflicts of interest.