Hematopoietic PBX-interacting protein mediates cartilage degeneration during the pathogenesis of osteoarthritis

Quanbo Ji, Xiaojie Xu, Lei Kang, Yameng Xu, Jingbo Xiao, Stuart B. Goodman, Xiang Zhu, Wenchao Li, Juan Liu, Xu Gao, Zhifeng Yan, Yuxuan Zheng, Zheng Wang (), William J. Maloney (), Qinong Ye () and Yan Wang ()
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Quanbo Ji: General Hospital of Chinese People’s Liberation Army
Xiaojie Xu: Beijing Institute of Biotechnology
Lei Kang: Peking University First Hospital
Yameng Xu: Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Jingbo Xiao: National Library of China
Stuart B. Goodman: Stanford University
Xiang Zhu: Beijing Institute of Biotechnology
Wenchao Li: General Hospital of Chinese People’s Liberation Army
Juan Liu: Beijing Institute of Biotechnology
Xu Gao: Johns Hopkins University School of Medicine
Zhifeng Yan: General Hospital of Chinese People’s Liberation Army
Yuxuan Zheng: Peking University
Zheng Wang: General Hospital of Chinese People’s Liberation Army
William J. Maloney: Stanford University
Qinong Ye: Beijing Institute of Biotechnology
Yan Wang: General Hospital of Chinese People’s Liberation Army

Nature Communications, 2019, vol. 10, issue 1, 1-15

Abstract: Abstract Osteoarthritis (OA) has been recognized as the most common chronic age-related disease. Cartilage degeneration influences OA therapy. Here we report that hematopoietic pre-B cell leukemia transcription factor-interacting protein (HPIP) is essential for OA development. Elevated HPIP levels are found in OA patients. Col2a1-CreERT2/HPIPf/f mice exhibit obvious skeletal abnormalities compared with their HPIPf/f littermates. HPIP deficiency in mice protects against developing OA. Moreover, intra-articular injection of adeno-associated virus carrying HPIP-specific short hairpin RNA in vivo attenuates OA histological signs. Notably, in vitro RNA-sequencing and chromatin immunoprecipitation sequencing profiles identify that HPIP modulates OA cartilage degeneration through transcriptional activation of Wnt target genes. Mechanistically, HPIP promotes the transcription of Wnt targets by interacting with lymphoid enhancer binding factor 1 (LEF1). Furthermore, HPIP potentiates the transcriptional activity of LEF1 and acetylates histone H3 lysine 56 in the promoters of Wnt targets, suggesting that HPIP is an attractive target in OA regulatory network.

Date: 2019
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DOI: 10.1038/s41467-018-08277-5

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