Details

Autor(en) / Beteiligte

• Tamashunas, Andrew C.
• Katiyar, Aditya
• Zhang, Qiao
• Purkayastha, Purboja
• Singh, Pankaj K.
• Chukkapalli, Sasanka S.
• Lele, Tanmay P.

Titel

Osteoprotegerin is sensitive to actomyosin tension in human periodontal ligament fibroblasts

Ist Teil von

• Journal of cellular physiology, 2021-08, Vol.236 (8), p.5715-5724

Ort / Verlag

United States: Wiley Subscription Services, Inc

Erscheinungsjahr

2021

Link zum Volltext

Quelle

Wiley Online Library (Online service)

Beschreibungen/Notizen

• 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. Graphical Although alveolar bone remodeling is well known to be caused by mechanical stresses generated on the periodontal ligament (PDL), the underlying mechanisms are poorly understood. Here we focus on a key cell type in the PDL, the periodontal ligament fibroblast (PdLF), which is known to be contractile and plays a key role in bone remodeling through expression of bone regulatory proteins. Because external mechanical stresses are balanced by modulation of intracellular actomyosin forces, we asked here if modulating intracellular contractility can by itself alter messenger RNA (mRNA) levels of key genes in human PdLFs. Disrupting different populations of actomyosin stress fibers by inhibiting myosin light chain kinase or Rho kinase which promote nonmuscle myosin II phosphorylation, altered mRNA levels of bone regulatory protein osteoprotegerin (OPG) and matrix metalloproteinases. Infection of PdLFs by two different types of periodontal bacteria (Porphyromonas gingivalis and Fusobacterium nucleatum) upregulated NMMII phosphorylation while downregulating OPG. Our results add in vitro support to the concept that PdLF tensional homeostasis may be crucial for its bone regulatory functions and may become dysregulated in the response to bacterial infection. They also highlight the importance of actomyosin tension in the overall process.