2. Academic Validation
  3. Lipoteichoic acid restrains macrophage senescence via β-catenin/FOXO1/REDD1 pathway in age-related osteoporosis

Lipoteichoic acid restrains macrophage senescence via β-catenin/FOXO1/REDD1 pathway in age-related osteoporosis

  • Aging Cell. 2023 Dec 21:e14072. doi: 10.1111/acel.14072.
Weike Cheng 1 2,  Yong Fu 1 2,  Zexin Lin 1 2,  Mouzhang Huang 1 2,  Yingqi Chen 1 2,  Yanjun Hu 1 2,  Qingrong Lin 1 2,  Bin Yu 1 2,  Guanqiao Liu 1 2
Affiliations

Affiliations

  • 1 Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou, China.
  • 2 Guangdong Provincial Key Laboratory of Bone and Cartilage Regenerative Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, China.
PMID: 38126583 DOI: 10.1111/acel.14072
Abstract

Osteoporosis and its related fractures are common causes of morbidity and mortality in older adults, but its underlying molecular and cellular mechanisms remain largely unknown. In this study, we found that lipoteichoic acid (LTA) treatment could ameliorate age-related bone degeneration and attenuate intramedullary macrophage senescence. FOXO1 signaling, which was downregulated and deactivated in aging macrophages, played a key role in the process. Blocking FOXO1 signaling caused decreased REDD1 expression and increased phosphorylation level of mTOR, a major driver of aging, as well as aggravated bone loss and deteriorated macrophage senescence. Moreover, LTA elevated FOXO1 signaling through β-catenin pathway while β-catenin inhibition significantly suppressed FOXO1 signaling, promoted senescence-related protein expression, and accelerated bone degeneration and macrophage senescence. Our findings indicated that β-catenin/FOXO1/REDD1 signaling plays a physiologically significant role that protecting macrophages from senescence during aging.

Keywords

FOXO1; REDD1; mTOR; macrophage senescence; osteoporosis; β-Catenin.

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