FAK Promotes Osteoblast Progenitor Cell Proliferation and Differentiation by Enhancing Wnt Signaling

Abstract

Decreased bone formation is often associated with increased bone marrow adiposity. The molecular mechanisms that are accountable for the negative correlation between bone mass and bone marrow adiposity are incompletely understood. Focal adhesion kinase (FAK) has critical functions in proliferation and differentiation of many cell types; however, its roles in osteoblast lineage cells are largely unknown. We show herein that mice lacking FAK in Osterix-expressing cells exhibited decreased osteoblast number and low bone mass as well as increased bone marrow adiposity. The decreased bone mass in FAK-deficient mice was accounted for by decreased proliferation, compromised osteogenic differentiation, and increased adipogenic differentiation of bone marrow Osterix-expressing cells resulting from downregulation of Wnt/β-catenin signaling due to the reduced expression of canonical Wnt ligands. In contrast, FAK loss in calvarial preosteoblasts had no adverse effect on their proliferation and osteogenic differentiation and these cells had intact Wnt/β-catenin signaling.

Tsc1 Regulates the Balance Between Osteoblast and Adipocyte Differentiation Through Autophagy/Notch1/β-Catenin Cascade

“…It has been demonstrated that core‐binding factor subunit beta controls the balance between osteoblast and adipocyte lineage through promoting Wnt/β‐catenin signaling . Similarly, we showed that focal adhesion kinase inhibits the adipogenic differentiation potential and enhances the osteogenic differentiation potential of BMSCs through enhancing β‐catenin signaling …”

“…Male Tsc1 F/F , Osx‐Cre, CHet, and CKO mice were euthanized at the age of 1 month ( n = 9 for each group). Femurs were analyzed by micro–computed tomography (μCT) as reported . In brief, the trabecular region of interest (ROI) from the distal femora was identified as 10% of the bone length starting at the interface between the growth plate and metaphyseal trabecular bone extending into the metaphysis.…”

“…Histomorphometry measurements were conducted as described . All measurements were performed following the published guidelines .…”

“…Briefly, bone marrow were flushed and cultured in α‐MEM with 10% FBS for 3 days and rinsed with medium to remove nonadherent cells. Adherent cells were cultured for 7 to 8 days as described …”

“…The medium was changed every other day. The alkaline phosphatase (ALP) staining and Alizarin Red (AR) staining was performed at day 7 and day 21, respectively, as described …”