Activation of peroxisome proliferator-activated receptor γ inhibits TNF-α-mediated osteoclast differentiation in human peripheral monocytes in part via suppression of monocyte chemoattractant protein-1 expression

PPAR-γ agonist rosiglitazone prevents inflammatory periodontal bone loss by inhibiting osteoclastogenesis

“…This finding is consistent with previous reports that both 15d-PGJ 2 and ciglitazone act as natural ligands and synthetic agonists for PPAR-γ, respectively, inhibiting TNF-α-induced osteoclast differentiation determined by TRAP staining [30]. Recently, Park et al [31] found that a novel PPAR-γ agonist, KR62776, suppressed the in vitro activation of TRAP expression in the M-CSF and RANKL-stimulated bone marrow mononuclear (BMM) cells.…”

Peroxisome proliferator-activated receptor gamma polymorphism is related to peak bone mass: the JPOS study

“…Similarly, Suzawa et al [8] demonstrated that PPARγ inhibition causes the cytokines interleukin 1 and tumor necrosis factor (TNF)-α to suppress adipogenesis in bone marrow stem cells and direct cellular differentiation toward osteoblasts. In contrast, other studies have reported that PPARγ promotes osteoblast activity [9,10]. Mbalaviele et al [9] reported that treatment of hematopoietic stem cells with a PPARγ agonist completely inhibited osteoclast formation associated with RANK signaling.…”

“…In explaining their findings, Mbalaviele et al [9] proposed that the inhibition of osteoclastogenesis may occur through PPARγ-associated antagonism of the nuclear factor κB pathway, with a resultant loss in RANK ligand (RANKL) signaling. A recent study by Hounoki et al [10] also found that activation of PPARγ inhibited TNF-α-induced osteoclastogenesis in human monocytes. The TNF-α-induced osteoclastogenesis was independent of RANKL-induced osteoclastogenesis [11,12].…”

The Free Fatty Acid Receptor G Protein-coupled Receptor 40 (GPR40) Protects from Bone Loss through Inhibition of Osteoclast Differentiation*

“…The effects of PPARs on osteoclastogenesis remain controversial and depend on the receptor subtype. PPAR␥ activation was found either to inhibit (32,33) or stimulate (34) osteoclast differentiation, whereas antisense strategies for PPAR␦/␤ revealed a pro-resorbing impact of these two isoforms (35). Interestingly, PPAR␥ agonists such as thiazolidinediones and rosiglitazone also stimulate GPR40 signaling pathways, therefore inhibition of osteoclastogenesis by PPAR␥ activators may in fact result from an uninvestigated GPR40 activation (25,36,37).…”