| First Author | Li S | Year | 2020 |
| Journal | Cell Death Dis | Volume | 11 |
| Issue | 9 | Pages | 762 |
| PubMed ID | 32938907 | Mgi Jnum | J:303375 |
| Mgi Id | MGI:6512126 | Doi | 10.1038/s41419-020-02947-3 |
| Citation | Li S, et al. (2020) PKC-delta deficiency in B cells displays osteopenia accompanied with upregulation of RANKL expression and osteoclast-osteoblast uncoupling. Cell Death Dis 11(9):762 |
| abstractText | PKC-delta is an important molecule for B-cell proliferation and tolerance. B cells have long been recognized to play a part in osteoimmunology and pathological bone loss. However, the role of B cells with PKC-delta deficiency in bone homeostasis and the underlying mechanisms are unknown. We generated mice with PKC-delta deletion selectively in B cells by crossing PKC-delta-loxP mice with CD19-Cre mice. We studied their bone phenotype using micro-CT and histology. Next, immune organs were obtained and analyzed. Western blotting was used to determine the RANKL/OPG ratio in vitro in B-cell cultures, ELISA assay and immunohistochemistry were used to analyze in vivo RANKL/OPG balance in serum and bone sections respectively. Finally, we utilized osteoclastogenesis to study osteoclast function via hydroxyapatite resorption assay, and isolated primary calvaria osteoblasts to investigate osteoblast proliferation and differentiation. We also investigated osteoclast and osteoblast biology in co-culture with B-cell supernatants. We found that mice with PKC-delta deficiency in B cells displayed an osteopenia phenotype in the trabecular and cortical compartment of long bones. In addition, PKC-delta deletion resulted in changes of trabecular bone structure in association with activation of osteoclast bone resorption and decrease in osteoblast parameters. As expected, inactivation of PKC-delta in B cells resulted in changes in spleen B-cell number, function, and distribution. Consistently, the RANKL/OPG ratio was elevated remarkably in B-cell culture, in the serum and in bone specimens after loss of PKC-delta in B cells. Finally, in vitro analysis revealed that PKC-delta ablation suppressed osteoclast differentiation and function but co-culture with B-cell supernatant reversed the suppression effect, as well as impaired osteoblast proliferation and function, indicative of osteoclast-osteoblast uncoupling. In conclusion, PKC-delta plays an important role in the interplay between B cells in the immune system and bone cells in the pathogenesis of bone lytic diseases. |
