Osteoporosis International

Bone mineral density (BMD) is the major factor for determining bone strength, which is closely correlated to osteoporotic fracture risk and is largely determined by multiple genetic factors. The RANK (TNFRSF11A), receptor for RANKL, is a member of the tumor necrosis factor receptor (TNFR) superfamily and plays a central role in osteoclast development. In order to investigate the effects of RANK polymorphism on BMD and osteoporosis, we directly sequenced the RANK gene in 24 Korean individuals and identified 25 sequence variants. Eleven of these polymorphisms were selected and genotyped in a larger-scale study of postmenopausal women (n = 560). Areal BMD (g/cm2) of the anterior–posterior lumbar spine and the nondominant proximal femur were measured using dual-energy X-ray absorptiometry. We found that two intronic polymorphisms in the RANK gene [RANK + 34863G > A (rs12458117) and RANK + 35928insdelC (new polymorphism found in this study) in intron 6] were significantly associated with the BMD of the lumbar spine, i.e., rare alleles were significantly associated with low BMD of the lumbar spine among Korean postmenopausal women (p = 0.04 and 0.02, respectively). These polymorphisms were also associated with low BMD of proximal femur sites, including Ward’s triangle, trochanter, and total femur. Our results suggest that +34863G > A and +35928insdelC polymorphisms in RANK are possible genetic factors for low BMD in postmenopausal women.

Bone-related diseases pose a major health burden for modern society. Bone is one of the organs that rely on stem cell function to maintain tissue homeostasis. Stem cell therapy has emerged as an effective new strategy to repair and replace damaged tissue. Although research on bone marrow mesenchymal stem cells has been conducted over the last few decades, the identity and definition of the true skeletal stem cell population remains controversial. Due to technological advances, some progress has been made in the prospective separation and function research of purified skeletal stem cells. Here, we reviewed the recent progress of highly purified skeletal stem cells, their function in bone development and repair, and the impact of aging on skeletal stem cells. Various studies on animal and human models distinguished and isolated skeletal stem cells using different surface markers based on flow-cytometry-activated cell sorting. The roles of different types of skeletal stem cells in bone growth, remodeling, and repair are gradually becoming clear. Thanks to technological advances, SSCs can be specifically identified and purified for functional testing and molecular analysis. The basic features of SSCs and their roles in bone development and repair and the effects of aging on SSCs are gradually being elucidated. Future mechanistic studies can help to develop new therapeutic interventions to improve various types of skeletal diseases and enhance the regenerative potential of SSCs.