Osteoprotegerin is sensitive to actomyosin tension in human periodontal ligament fibroblasts

Abstract

Periodontal ligament fibroblasts (PdLFs) are an elongated cell type in the periodontium with matrix and bone regulatory functions which become abnormal in periodontal disease (PD). Here we found that the normally elongated and oriented PdLF nucleus becomes rounded and loses orientation in a mouse model of PD. Using in vitro micropatterning of cultured primary PdLF cell shape, we show that PdLF elongation correlates with nuclear elongation and the presence of thicker, contractile F‐actin fibers. The rounded nuclei in mouse PD models in vivo are, therefore, indicative of reduced actomyosin tension. Inhibiting actomyosin contractility by inhibiting myosin light chain kinase, Rho kinase or myosin ATPase activity, in cultured PdLFs each consistently reduced messenger RNA levels of bone regulatory protein osteoprotegerin (OPG). Infection of cultured PdLFs with two different types of periodontal bacteria (Porphyromonas gingivalis and Fusobacterium nucleatum) failed to recapitulate the observed nuclear rounding in vivo, upregulated nonmuscle myosin II phosphorylation and downregulated OPG. Collectively, our results add support to the hypothesis that PdLF contractility becomes decreased and contributes to disease progression in PD.

Effects of secretome derived from macrophages exposed to calcium oxalate crystals on renal fibroblast activation

“…The activation of renal fibroblasts is also characterized by up-regulations of α-SMA and F-actin incorporated into the stress fibers 66 – 68 . During the transition of fibroblasts from quiescent state to their activated form, up-regulations of α-SMA and F-actin have been reported to promote myofibroblast contractile activity 67 , 69 . Several lines of evidence have indicated that α-SMA-associated contraction is involved in ECM organization 67 , 70 , 71 .…”

Periodontal disease and emerging point-of-care technologies for its diagnosis

“…Consequently, the study concluded that OPG is responsive to actomyosin tension in human periodontal ligament fibroblasts. 55 a. Cytokines. PD is a chronic inflammatory disease initiated by microbial dysbiosis.…”

From the Matrix to the Nucleus and Back: Mechanobiology in the Light of Health, Pathologies, and Regeneration of Oral Periodontal Tissues

“…Periodontal disease also leads to round PDLF nuclear morphology in vivo, which is accompanied by a reduction in actomyosin contractility and a decrease in OPG synthesis from PDLFs. This additional mechanism might, therefore, contribute to this shift in biochemical signaling and is a direct consequence of disturbed MT (Figure 4) [265].…”