Abstract
A balance between bone formation by osteoblasts and bone resorption by osteoclasts is necessary to maintain bone health and homeostasis. As a cancer of plasma cells, multiple myeloma (MM) is accompanied with rapid bone loss and fragility fracture. Bortezomib has been used as a first-line for treating MM for decades. Recently, the potential protection of bortezomib on osteoporosis (OP) is reported; however, the specific mechanism involving bortezomib-mediated antiosteoporotic effect is undetermined. In the present study, we assessed the effects of in vitro bortezomib treatment on osteogenesis and osteoclastogenesis and the protective effect on bone loss in ovariectomized (OVX) mice. Our results indicated that bortezomib treatment increased osteogenic differentiation of MC3T3-E1 cells as evidenced by increased levels of matrix mineralization and osteoblast-specific markers. In bortezomib-treated bone marrow monocytes (BMMs), osteoclast differentiation was suppressed, substantiated by downregulated tartrate-resistant acid phosphatase- (TRAP-) positive multinucleated cells, areas of actin rings, pit formation, and osteoclast-specific genes. Mechanistically, bortezomib exerted a protective effect against OP through the Smad ubiquitination regulatory factor- (SMURF-) mediated ubiquitination pathway. Furthermore, in vivo intraperitoneal injection of bortezomib attenuated the bone microarchitecture in OVX mice. Accordingly, our findings corroborated that bortezomib might have future applications in the treatment of postmenopausal OP.
Highlights
Osteoporosis (OP) is a progressive metabolic disease manifested as degeneration of bone structure and impaired bone mass [1]
OP can be divided into two subtypes: estrogen-deficient OP and senile OP based on the etiology, the collective driving factor is disrupted homeostasis between bone formation and bone resorption [4]
Quantitative analysis indicated that bortezomib treatment increased the Alkaline Phosphatase (ALP) activity in MC3T3-E1 cells by 26.5% (Figure 1(b))
Summary
Osteoporosis (OP) is a progressive metabolic disease manifested as degeneration of bone structure and impaired bone mass [1]. Severe OP is accompanied by increased bone fragility, leading to increased risks of osteoporotic vertebral compression fracture (OVCF) and hip fracture [3], associated with considerable morbidity and mortality. OP can be divided into two subtypes: estrogen-deficient OP and senile OP based on the etiology, the collective driving factor is disrupted homeostasis between bone formation and bone resorption [4]. An osteoblast/osteocyte-induced osteogenesis shift toward overactivated osteoclast-mediated osteoclastogenesis can lead to excessive bone loss and microarchitectural impairment [5]. Targeting the regulation of bone metabolism is essential for reversing the progression of OP
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
