Abstract
Senile osteoporosis can cause bone fragility and increased fracture risks and has been one of the most prevalent and severe diseases affecting the elderly population. Bone formation depends on the proper osteogenic differentiation of bone marrow stromal cells (BMSCs) in the bone marrow microenvironment, which is generated by the functional relationship among different cell types in the bone marrow. With aging, bone marrow provides signals that repress osteogenesis. Finding the signals that oppose BMSC osteogenic differentiation from the bone marrow microenvironment and identifying the abnormal changes in BMSCs with aging are key to elucidating the mechanisms of senile osteoporosis. In a pilot experiment, we found that 4-1BBL and 4-1BB were more abundant in bone marrow from aged (18-month-old) mice than young (6-month-old) mice. Meanwhile, significant bone loss was observed in aged mice compared with young mice. However, very little data have been generated regarding whether high-level 4-1BB/4-1BBL in bone marrow was associated with bone loss in aged mice. In the current study, we found upregulation of 4-1BB in the BMSCs of aged mice, which resulted in the attenuation of the osteogenic differentiation potential of BMSCs from aged mice via the p38 MAPK-Dkk1 pathway. More importantly, bone loss of aged mice could be rescued through the blockade of 4-1BB signaling in vivo. Our study will benefit not only our understanding of the pathogenesis of age-related trabecular bone loss but also the search for new targets to treat senile osteoporosis.
Highlights
Osteoporosis is defined as a deterioration of bone mass and microarchitecture with increasing fragility, which leads to fractures[1]
We focused on the role of 4-1BB/4-1BBL signaling in bone marrow stromal cells (BMSCs) osteogenic differentiation and osteoporosis pathophysiology
We found that 4-1BB was upregulated in BMSCs from aged mice, which resulted in the attenuation of osteogenic differentiation potential of BMSCs of aged mice via the p38 MAPK-Dkk[1] signaling pathway
Summary
Osteoporosis is defined as a deterioration of bone mass and microarchitecture with increasing fragility, which leads to fractures[1]. There are two main pathophysiological processes that can result in significant bone loss. The first is known as postmenopausal osteoporosis, which is derived from estrogen deprivation[2]. A second type of osteoporosis, known as senile osteoporosis, most frequently affects older people, predisposing them to hip fractures[3]. The skeleton is composed of two components: peripheral and axial. The axial skeleton is composed of trabecular (cancellous) bone. Because bone marrow elements are the source of cells involved in bone turnover, the proximity to the cellular elements results in earlier and more sensitive responses by trabecular bone to whole-body changes in the bone remodeling rate[4]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
