Altered morpho-functional features of bones in autoimmune disease-prone BXSB/MpJ- Yaa mice

Abstract

Bones play crucial roles in motility, electrolyte metabolism, and immunity. Clinical cases have suggested bone dysfunction in several systemic autoimmune diseases. This study exhibited altered bone morpho-functions in BXSB/MpJ-Yaa as a murine autoimmune disease model. During clinical examinations, the serum Ca level was significantly higher in BXSB/MpJ-Yaa than the healthy control BXSB/MpJ at the early stage (two to four months), but that in BXSB/MpJ-Yaa decreased with advancing age. Further, the increase of urinary Ca with nephritis and white blood cells with mild anemia proceeded in BXSB/MpJ-Yaa with advancing age. The thyroid and parathyroid gland morphologies and serum parathormone level did not differ among strains, but the tibia was smaller in BXSB/MpJ-Yaa than in BXSB/MpJ especially during the late stage (six months). Histologically, osteoclasts and osteoblasts showed increased and decreased tendencies, respectively, in BXSB/MpJ-Yaa during the early stage, and osteoclasts and bone area significantly increased and decreased, respectively, compared with BXSB/MpJ at later stages. The bone morphological indices were affected by the expression of BXSB/MpJ-Yaa mutation genes and inflammatory genes in BXSB/MpJ-Yaa. In conclusion, systemic autoimmune diseases in BXSB/MpJ-Yaa are associated with the morpho-functional abnormalities of bones, calcium dynamics, and hematopoiesis, and each factor contributes to forming the phenotypes in this disease.

Impact statement

Bone disease, such as osteoporosis and rheumatoid arthritis, increases because of the progression of an aging society. Autoimmune disease are important and predisposing factors for the pathogenesis of the bone disease; however, the pathological mechanism is unclear. We have demonstrated that systemic autoimmune disease in BXSB/MpJ-Yaa is closely associated with the morpho-functional abnormalities of bones including bone marrow and has complicated pathology. The abnormalities are characterized by altered regulations of serum calcium, anemia tendency, and hematopoiesis with increased WBCs and decreased PLs, short length and low mass of long bones, imbalance in the populations of osteoclasts and osteoblasts, and increased expression of candidate genes for causing and/or exacerbating their phenotypes. Therefore, BXSB/MpJ-Yaa serves as a model to elucidate bone phenotypes in systemic autoimmune disease that would be affected by the factors in the bone as well as the other immune and/or mineral metabolism organs both in human and experimental medicine.