Osteoporosis: the current status of mesenchymal stem cell-based therapy

Abstract

Osteoporosis, or bone loss, is a progressive, systemic skeletal disease that affects millions of people worldwide. Osteoporosis is generally age related, and it is underdiagnosed because it remains asymptomatic for several years until the development of fractures that confine daily life activities, particularly in elderly people. Most patients with osteoporotic fractures become bedridden and are in a life-threatening state. The consequences of fracture can be devastating, leading to substantial morbidity and mortality of the patients. The normal physiologic process of bone remodeling involves a balance between bone resorption and bone formation during early adulthood. In osteoporosis, this process becomes imbalanced, resulting in gradual losses of bone mass and density due to enhanced bone resorption and/or inadequate bone formation. Several growth factors underlying age-related osteoporosis and their signaling pathways have been identified, such as osteoprotegerin (OPG)/receptor activator of nuclear factor B (RANK)/RANK ligand (RANKL), bone morphogenetic protein (BMP), wingless-type MMTV integration site family (Wnt) proteins and signaling through parathyroid hormone receptors. In addition, the pathogenesis of osteoporosis has been connected to genetics. The current treatment of osteoporosis predominantly consists of antiresorptive and anabolic agents; however, the serious adverse effects of using these drugs are of concern. Cell-based replacement therapy via the use of mesenchymal stem cells (MSCs) may become one of the strategies for osteoporosis treatment in the future.

PCE17 and its active compounds exert an anti-osteoporotic effect through the regulation of receptor activator of nuclear factor-κB ligand in ovariectomized mice

“…Osteoclasts play important roles in pathological bone loss and bone resorption (Xu et al, ). RANKL bind to RANK, and thus, induces the differentiation and activation of osteoclast through several downstream signaling pathways, including nuclear factor‐κB (Phetfong et al, ). Furthermore, RANKL‐deficient mice show thickened bones, due to a defect in osteoclast differentiation (Jones et al, ), and Okamatsu et al () reported that anti‐RANKL antibody reduced TRAP levels (an osteoclast marker) and increased bone mass.…”

“…Osteoporosis causes reductions in bone mineral density, and consequently increases the risk of fracture (Phetfong et al, ). The prevalence of the disease has dramatically risen and it now affects a wide segment of the elderly population in industrialized countries, and thus, imposes a heavy socioeconomic burden as a result of increased frailty and mortality (Portal‐Núñez, Mediero, Esbrit, Sánchez‐Pernaute, Largo, & Herrero‐Beaumont, ).…”

Hormonal and Genetic Role Affecting the Bone Resorption in Patients with Osteoporosis

“…Taniguchi believes that calcium phosphatase can directly activate the expression of the gene [22]. Interferon beta can cause decreased levels of calcium phosphatase, thus pressing the osteoclast function [31].…”

“…Through this path, changes in the inner and external environment of the body will cause an adjustment to the secretion of thyroxine hormones in the form of T4 (tetraiodotironin) and T3 (triiodotironin). Except for producing thyroxin, the thyroid gland also produces the hormone calcitonin, a hormone whose effect lowers blood calcium levels [31].…”

Inhibition of the mitochondrial permeability transition exerts sex-specific stimulatory effect on fracture repair

“…The incidence of bone fractures is increasing worldwide as a function of the growth of the aged population over 50 years old with osteoporosis and increased bone fragility (1). Currently, 5-10 % of fractures result in fracture non-unions, a condition in which few bone-anabolic treatment modalities have proven effective (2).…”