High bone microarchitecture, strength, and resistance to bone loss in MRL/MpJ mice correlates with activation of different signaling pathways and systemic factors. Issue 1 (27th November 2019)

• Record Type: Journal Article
• Authors: Sun, Xuying; Gao, Xueqin; Deng, Zhenhan; Zhang, Linlin; McGilvray, Kirk; Gadomski, Benjamin C.; Amra, Sarah; Bao, Gang; Huard, Johnny
• Is Part Of: FASEB journal. Volume 34:Issue 1(2020)
• Page Start: 789
• Page End: 806
• Publication Date: 2019-11-27
• Subjects: MRL/MpJ mice -- osteoblasts -- osteoclasts -- ovariectomy -- tibia fracture; Biology -- Periodicals; Biology, Experimental -- Periodicals; 570
• DOI: 10.1096/fj.201901229RR
• Languages: English
• ISSNs: 0892-6638

Abstract

Abstract: The MRL/MpJ mice have demonstrated an enhanced tissue regeneration capacity for various tissues. In the present study, we systematically characterized bone microarchitecture and found that MRL/MpJ mice exhibit higher bone microarchitecture and strength compared to both C57BL/10J and C57BL/6J WT mice at 2, 4, and 10 months of age. The higher bone mass in MRL/MpJ mice was correlated to increased osteoblasts, decreased osteoclasts, higher cell proliferation, and bone formation, and enhanced pSMAD5 signaling earlier during postnatal development (2‐month old) in the spine trabecular bone, and lower bone resorption rate at later age. Furthermore, these mice exhibit accelerated fracture healing via enhanced pSMAD5, pAKT and p‐P38MAPK pathways compared to control groups. Moreover, MRL/MpJ mice demonstrated resistance to ovariectomy‐induced bone loss as evidenced by maintaining higher bone volume/tissue volume (BV/TV) and lower percentage of bone loss later after ovariectomy. The consistently higher serum IGF1 level and lower RANKL level in MRL/MpJ mice may contribute to the maintenance of high bone mass in uninjured and injured bone. In conclusion, our results indicate that enhanced pSMAD5, pAKT, and p‐P38MAPK signaling, higher serum IGF‐1, and lower RANKL level contribute to the higher bone microarchitecture and strength, accelerated healing, and resistance to osteoporosis in MRL/MpJ mice.