ArticleCurrent medical science2026
LATS1/2 Inhibitor Attenuates Osteoclast Differentiation via Hippo-YAP/TAZ Signaling Pathway and Alleviates Osteoporosis in Ovariectomized Rats.
Article in Current medical science, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundThis study investigated the role and underlying mechanism of large tumor suppressor 1/2 (LATS1/2), a core kinase in the Hippo pathway, in inhibiting osteoclastic differentiation and ameliorating ovariectomy (OVX)-induced osteoporosis in rats through the RANKL-dependent Hippo-YAP/TAZ signaling pathway both in vivo and in vitro.
methodsUnder stimulation by receptor activator of nuclear factor-κB ligand (RANKL), small interfering RNA (siRNA) was used to suppress the expression of LATS1/2 and YAP. The levels of osteoclast-related genes and proteins, as well as YAP pathway proteins, were evaluated in RAW264.7 cells and bone marrow-derived macrophages (BMMs) via quantitative reverse transcription polymerase chain reaction and Western blot analysis. Cell viability and osteoclast formation potential were measured via the Cell Counting Kit-8 assay and tartrate-resistant acid phosphatase (TRAP) staining, respectively. Osteoclasts and filamentous actin were stained with TRAP and phalloidin to characterize cell morphology. Furthermore, to research the role of the Hippo/YAP pathway, we used siRNA to knock down LATS1/2 and examined its effect on RANKL-mediated osteoclast differentiation. In addition, we constructed an OVX-induced osteoporosis model in 8-week-old female Sprague‒Dawley rats, treated them with a LATS1/2 inhibitor for 4 weeks at 12 weeks after surgery, and evaluated the remission of osteoporosis by micro-CT and histological methods with a LATS1/2 inhibitor.
resultsAfter LATS1/2 was silenced or inhibited in BMMs and RAW264.7 cells, YAP was significantly upregulated and YAP phosphorylation and osteoclast function were inhibited. By interfering with YAP expression, the Hippo/YAP pathway inhibited osteoclast differentiation in BMMs. In vivo, injection of LATS1/2 inhibitor alleviated osteoporosis in ovariectomized rats.
conclusionOur findings indicate that the inhibition of LATS1/2 considerably suppresses osteoclast differentiation and alleviates OVX-induced osteoporosis in rats. Additionally, our results show that LATS1/2 inhibitors are important for the differentiation of osteoclasts and highlight the possible therapeutic value of LATS1/2 inhibitors.
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