Journal Article

The alterations of molecular repertoire of the RANKL-induced osteoclastogenesis in the M1 macrophage-derived inflammatory milieu

Chen, Ching-Yun, Chen, Yu-Hsu, Yu, Ching-Hsiao, Wu, Chun-Shan, Yang, Chin-Hua, Chen, Shau-Kwaun, Hsu, Yu-Pao

2025

Overview

Inflammation have been linked to bone diseases such as osteoporosis or bone destruction. However, whether M1 inflammatory stimuli exert a stimulatory or inhibitory effect on the differentiation of osteoclasts remained controversial. Also, how inflammatory milieu influence cell proliferation and survival during osteoclastogenesis have not been determined. Here we reported the molecular repertoire alterations of RANKL-stimulated osteoclastogenesis from RAW264.7 at different stages in the inflammatory environments. Adding conditioned medium collected from LPS-stimulated macrophage, which are the primary source of extracellular inflammatory mediators, resulted in a biphasic change in cell number among differentiating preosteoclasts. The inflammatory milieu induced a transient proliferation of preosteoclasts during the initial 48 h, which was followed by a significant decline in cell numbers from the fourth day onwards. Proliferation-related AKT and ERK were transiently activated in the inflammatory environments, which also upregulated the expressions of c-myc , a major transcription factor for osteoclast differentiation, and pro-inflammatory genes, such as Tnf-a and Nos2 . Following prolonged exposure to an inflammatory environment, undifferentiated osteoclast precursors undergo apoptosis. Our findings suggest that short-term inflammatory exposure transiently promotes the proliferation and differentiation of preosteoclasts, whereas long-term exposure leads to apoptosis, potentially due to the enhancement of inflammatory signals.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 631/337 / 631/45 / AKT protein / Animals / Apoptosis / Apoptosis - drug effects / Bone diseases / c-Myc protein / Cell differentiation / Cell Differentiation - drug effects / Cell number / Cell proliferation / Cell Proliferation - drug effects / Cell survival / Culture Media, Conditioned - pharmacology / Humanities and Social Sciences / Inflammation / Inflammation - metabolism / Inflammation - pathology / Inflammatory milieu / Lipopolysaccharides - pharmacology / Macrophages / Macrophages - drug effects / Macrophages - metabolism / Mice / multidisciplinary / Myc protein / Osteoclastogenesis / Osteoclasts / Osteoclasts - cytology / Osteoclasts - drug effects / Osteoclasts - metabolism / Osteogenesis - drug effects / Osteoporosis / Osteoprogenitor cells / Pro-inflammatory cytokines / RANK Ligand - metabolism / RANK Ligand - pharmacology / RAW 264.7 Cells / Science / Science (multidisciplinary) / Signal Transduction / TRANCE protein / Transcription factors