Abnormal miR-145-5p expression impairs osteocytogenic differentiation through β-catenin signaling pathway in Adolescent Idiopathic Scoliosis
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摘要Abstract Introduction: Adolescent Idiopathic Scoliosis (AIS) is a three-dimensional spinal deformity of unclear etiopathogenesis with prevalence of 1-4% worldwide. Among various proposed pathomechanisms, systemic low bone mineral density (BMD) was observed in 30-38% of AIS patients and found to be one of the significant prognostic factors for curve progression. In last ORS 2016 meeting, we reported pathological structural changes in osteocyte lacuno-canalicular network (LCN) in AIS with more roundish lacuna (osteocyte body), shorter and less canaliculi (dendrites), and reduced sclerostin secretion suggesting impaired osteocytes connectivity and activity. Osteocytes, the descendant of osteoblasts, are abundant bone cells responsible for mechanosensation and orchestrate bone metabolism through LCN-aided cell to cell communication and paracrine/endocrine signaling. Sclerostin inhibits bone formation through antagonizing Wnt/ β-catenin signaling. In addition, cumulative evidence suggested that abnormal activation of β-catenin could also suppress osteocytogenesis and result in lower bone mass(1,2). Further study by our group found consistent overexpression of active β-catenin in bone lining cells with immunostaining in bone biopsy and in AIS primary osteoblasts culture in vitro (unpublished data), suggesting an endogenous phenomenon and providing a platform to look for potential upstream regulators. microRNA (miR) are short non-coding nucleotides that
have regulatory role on genes and proteins expression. The biological role of miR has been reported in various diseases, but rarely in AIS. In this study, we aimed to investigate the role of miR in osteocytogenic differentiation of AIS with a validated collagen-based 3D primary osteocytes culture model.
著者Jia-jun Zhang, Huan-xiong Chen, Elisa Man-shan Tam, Gene Chi-wai Man, Tsz-ping Lam, Simon KM Lee, Bobby KW Ng, Jack CY Cheng, Wayne YW Lee
會議名稱Orthopaedic Research Society 2017 Annual Meeting (ORS 2017)
會議地點San Diego, California, USA

上次更新時間 2018-18-01 於 08:21