Premium
Progranulin promotes bone fracture healing via TNFR pathways in mice with type 2 diabetes mellitus
Author(s) -
Ding Yuanjing,
Wei Jianlu,
Hettinghouse Aubryanna,
Li Guangfei,
Li Xin,
Einhorn Thomas A.,
Liu Chuanju
Publication year - 2021
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/nyas.14568
Subject(s) - bone healing , endochondral ossification , medicine , endocrinology , bone remodeling , type 2 diabetes mellitus , inflammation , bone fracture , osteoblast , diabetes mellitus , biology , cartilage , in vitro , surgery , anatomy , biochemistry , radiology
Type 2 diabetes mellitus (T2DM) significantly increases bone fragility and fracture risk. Progranulin (PGRN) promotes bone fracture healing in both physiological and type 1 diabetic conditions. The present study aimed to investigate the role of PGRN in T2DM bone fracture healing. MKR mice (with an FVB/N genetic background) were used as the T2DM model. Drill‐hole and Bonnarens and Einhorn models were used to investigate the role of PGRN in T2DM fracture healing in vivo . Primary bone marrow cells were isolated for molecular and signaling studies, and reverse transcription‐polymerase chain reaction, immunohistochemical staining, and western blotting were performed to assess PGRN effects in vitro . PGRN mRNA and protein expression were upregulated in the T2DM model. Local administration of recombinant PGRN effectively promoted T2DM bone fracture healing in vivo . Additionally, PGRN could induce anabolic metabolism during endochondral ossification through the TNFR2–Akt and Erk1/2 pathways. Furthermore, PGRN showed anti‐inflammatory activity in the T2DM bone regeneration process. These findings suggest that local administration of exogenous PGRN may be an alternative strategy to support bone regeneration in patients with T2DM. Additionally, PGRN might hold therapeutic potential for other TNFR‐related metabolic disorders.