UBAP2 plays a role in bone homeostasis through the regulation of osteoblastogenesis and osteoclastogenesis

Abstract

Osteoporosis is a condition characterized by decreased bone mineral density (BMD) and reduced bone strength, leading to an increased risk of fractures. Here, to identify novel risk variants for susceptibility to osteoporosis-related traits, an exome-wide association study is performed with 6,485 exonic single nucleotide polymorphisms (SNPs) in 2,666 women of two Korean study cohorts. The rs2781 SNP in UBAP2 gene is suggestively associated with osteoporosis and BMD with p-values of 6.1 × 10−7 (odds ratio = 1.72) and 1.1 × 10−7 in the case-control and quantitative analyzes, respectively. Knockdown of Ubap2 in mouse cells decreases osteoblastogenesis and increases osteoclastogenesis, and knockdown of ubap2 in zebrafish reveals abnormal bone formation. Ubap2 expression is associated with E-cadherin (Cdh1) and Fra1 (Fosl1) expression in the osteclastogenesis-induced monocytes. UBAP2 mRNA levels are significantly reduced in bone marrow, but increased in peripheral blood, from women with osteoporosis compared to controls. UBAP2 protein level is correlated with the blood plasma level of the representative osteoporosis biomarker osteocalcin. These results suggest that UBAP2 has a critical role in bone homeostasis through the regulation of bone remodeling.

Tricarboxylic Acid Cycle Regulation of Metabolic Program, Redox System, and Epigenetic Remodeling for Bone Health and Disease

“…Osteocytes play an important role in sclerostin production and transmit biomechanical or biophysical stimulation for bone mass homeostasis [1]. Under menopause, aging, hyperglycemia, or chronic inflammation conditions, bone remodeling goes far beyond mineral acquisition, turning the well-arranged bone trabecular network into a porous microstructure to accelerate the development of osteoporosis [3]. The fragile biomechanical features put the osteoporotic skeleton under an incredibly high risk of fracture, accounting for the leading cause of skeletal disability associated with premature mortality in the geriatric population [4,5].…”

Atsttrin regulates osteoblastogenesis and osteoclastogenesis through the TNFR pathway

“…Bone matrix homeostasis is a dynamically balanced system that is maintained by a balance between bone formation by osteoblasts and bone resorption by osteoclasts 1 , 2 . Osteoblasts are derived from mesenchymal precursor cells and are responsible for the deposition of new bone matrix to facilitate bone mineralization during bone reconstruction 3 , 4 .…”