DUSP26 Regulated by YY1 Lactylation Couples Osteogenesis and Angiogenesis by Dephosphorylating PMPCB at Y141 and Activating Mitophagy in BMSCs.
- 1Department of Orthopedic Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
- 2Department of Ultrasound, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
- 3Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
Abstract
Bone marrow mesenchymal stem cells (BMSCs) support bone formation through osteogenic differentiation and pro-angiogenic paracrine activity, but the mechanisms coordinating these functions remain incompletely understood. Here, we identified dual-specificity phosphatase 26 (DUSP26) as a regulator of BMSC osteogenesis and mitochondrial homeostasis. DUSP26 expression increased during osteogenic differentiation and was reduced in osteoporotic femoral tissues. p300 gain- and loss-of-function experiments, together with analysis of the Yin Yang1(YY1) K183R mutant, supported the conclusion that p300-regulated YY1 lactylation contributes to DUSP26 transcriptional activation. DUSP26 interacted with the mitochondrial processing peptidase subunit beta(PMPCB) and reduced its tyrosine phosphorylation, with mass spectrometry and mutational analyses implicating Y141 as involved in this regulation. Functional assays supported a model in which DUSP26 limits mitochondrial processing peptidase (MPP)-mediated PTEN-induced kinase 1 (PINK1) processing and promotes PINK1-dependent mitophagy, thereby supporting mitochondrial homeostasis. DUSP26 enhanced osteogenic differentiation and the pro-angiogenic activity of BMSC-conditioned medium(CM), whereas its knockdown impaired bone formation and reduced type H vessels in vivo. Furthermore, BMSC-derived exosomes carrying a runt-related transcription factor 2 (RUNX2) promoter-driven DUSP26 plasmid produced preferential transgene expression in osteogenic-lineage cells and attenuated ovariectomy-induced bone loss in mice. These findings link lactylation-associated transcriptional regulation to mitochondrial protein processing and support further preclinical evaluation of DUSP26-directed approaches for osteoporosis.
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BibTeX
@article{lv2026dusp26,
title = {{DUSP26 Regulated by YY1 Lactylation Couples Osteogenesis and Angiogenesis by Dephosphorylating PMPCB at Y141 and Activating Mitophagy in BMSCs.}},
author = {Yunpeng Lv and Feng Wu and Xiongjie Liang and Chong Liu and Wenhui Guo and Kejian Zhang and Jiawen Niu and Wenjie Jiang and Hongjian Xu and Anlong Jiang and Yang Zheng and Enming Yu and Xintao Wang and Jinglong Yan and Jingjun Xia and Chengchao Song},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
year = {2026},
month = oct,
doi = {10.1002/advs.78514},
url = {https://europepmc.org/article/MED/42949792},
note = {CC BY},
}
RIS
TY - JOUR
TI - DUSP26 Regulated by YY1 Lactylation Couples Osteogenesis and Angiogenesis by Dephosphorylating PMPCB at Y141 and Activating Mitophagy in BMSCs.
AU - Yunpeng Lv
AU - Feng Wu
AU - Xiongjie Liang
AU - Chong Liu
AU - Wenhui Guo
AU - Kejian Zhang
AU - Jiawen Niu
AU - Wenjie Jiang
AU - Hongjian Xu
AU - Anlong Jiang
AU - Yang Zheng
AU - Enming Yu
AU - Xintao Wang
AU - Jinglong Yan
AU - Jingjun Xia
AU - Chengchao Song
PY - 2026
DA - 2026/10/28
JO - Advanced science (Weinheim, Baden-Wurttemberg, Germany)
DO - 10.1002/advs.78514
UR - https://europepmc.org/article/MED/42949792
AB - Bone marrow mesenchymal stem cells (BMSCs) support bone formation through osteogenic differentiation and pro-angiogenic paracrine activity, but the mechanisms coordinating these functions remain incompletely understood. Here, we identified dual-specificity phosphatase 26 (DUSP26) as a regulator of BMSC osteogenesis and mitochondrial homeostasis. DUSP26 expression increased during osteogenic differentiation and was reduced in osteoporotic femoral tissues. p300 gain- and loss-of-function experiments, together with analysis of the Yin Yang1(YY1) K183R mutant, supported the conclusion that p300-regulated YY1 lactylation contributes to DUSP26 transcriptional activation. DUSP26 interacted with the mitochondrial processing peptidase subunit beta(PMPCB) and reduced its tyrosine phosphorylation, with mass spectrometry and mutational analyses implicating Y141 as involved in this regulation. Functional assays supported a model in which DUSP26 limits mitochondrial processing peptidase (MPP)-mediated PTEN-induced kinase 1 (PINK1) processing and promotes PINK1-dependent mitophagy, thereby supporting mitochondrial homeostasis. DUSP26 enhanced osteogenic differentiation and the pro-angiogenic activity of BMSC-conditioned medium(CM), whereas its knockdown impaired bone formation and reduced type H vessels in vivo. Furthermore, BMSC-derived exosomes carrying a runt-related transcription factor 2 (RUNX2) promoter-driven DUSP26 plasmid produced preferential transgene expression in osteogenic-lineage cells and attenuated ovariectomy-induced bone loss in mice. These findings link lactylation-associated transcriptional regulation to mitochondrial protein processing and support further preclinical evaluation of DUSP26-directed approaches for osteoporosis.
SN - 2198-3844
ER -