Kidney Week

Abstract: FR-PO516

Inflammation and Bone Loss in Patients with New Onset of Lupus Nephritis: The Pathways to Increased Osteoclastogenesis

Session Information

• Bone and Mineral Metabolism: Basic
  October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Bone and Mineral Metabolism

• 401 Bone and Mineral Metabolism: Basic

Authors

• De Lima, Ana Paula Calheiros, Universidade de São Paulo, São Paulo, Brazil

Ana Paula Calheiros De Lima,

• Dominguez, Wagner, University of Sao Paulo - Medical School - Nephrology Division, Sao Paulo, Brazil

Wagner Dominguez,

• Dias, Cristiane B., University of Sao Paulo, Brazil, São Paulo, Brazil

Cristiane B. Dias,

• dos Reis, Luciene, University of Sao Paulo - Medical School - Nephrology Division, Sao Paulo, Brazil

Luciene dos Reis,

• Jorgetti, Vanda, Universidade de Sao Paulo, Sao Paulo, Brazil

Vanda Jorgetti,

• Woronik, Viktoria, University of São Paulo, São Paulo, São paulo, Brazil

Viktoria Woronik,

Background

The pathogenesis of lupus nephritis (LN) comprises immune complexes deposition, abnormalities of complement system,T,B and regulatory cells-TREG, unbalance of Th1/Th2 subsets and IL17. Bone loss is present in newly diagnosed LN patients without an expressive dose of corticosteroids. Some evidences indicate an increased osteoclastogenesis as the main disturb of the remodeling process. Although the pathways that lead to bone loss are not completely understood, some systems are involved such as RANK-L/OPG, Wnt/βcatenin and Th17/IL17. In this context osteoblasts seems to play a remarkable role in mediating the crosstalk between bone and immune systems as well as osteoclast response. Vitamin D (VitD) is well-known for its role in bone mineralization but studies have been revealing its anti-inflammatory actions such as redirecting Th1 to Th2 response, suppressing Th17 and stimulating TREG. This study aimed to determine the pathways involved in abnormal osteoclastogenesis observed in women at the diagnosis of proliferative LN as well as evaluating if vitD can reverse this response.

Methods

We cultured the human osteoblastic cell line hFOB 1.19. Once mature, we divided cultures into those supplemented with serum from healthy controls (n=15) and LN patients (n-15) instead of fetal bovine serum. Then 1,25-dihydroxyvitaminD was added in two subgroups at 10^-9M e 10^-7M while vitD was absent in one subgroup in both healthy and LN women. After 48h of vitD addition, hFOB cultures were trypsinized. Flow Cytometry and multiplex assays were performed to test CD166, CD54, RANK-L, OPG, CD14, TLR4, NFκB, SOST, DKK1, βcatenin, IL6, IL1β, TNFα, IL2, IL17A, IL17F, IL21 and IL22.

Results

There was a tendency of DKK1 to be higher in LN patients than healthy controls at baseline without vitD (668.6x460.4pg/mg, p0.07) but at vitD 10^-7M the difference became significant (673.0x456.6pg/mg, p0.02). Without vitD, OPG was higher in the healthy group than LN (298.7x 178.8pg/mg, p0.003).

Conclusion

Osteoblasts cultured with LN serum tend to have lower levels of OPG, which can corroborate to increased osteoclastogenesis by inhibition of RANK-L action. Although DKK-1, an inhibitor of wnt/βcatenin pathway, tend to be higher in osteoblasts cultured with LN serum, no difference was observed in βcatenin levels among the groups.