Abnormal functions of osteocyte-lacuno- canalicular system in Adolescent Idiopathic Scoliosis
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AbstractIntroduction: Adolescent Idiopathic Scoliosis (AIS) is a complex three-dimensional (3D) spinal deformity of unknown etiology. Abnormal low bone mass was found in over 30% of AIS subjects. Osteocytes, the most abundant bone cells, regulated bone mineralization through interconnecting osteocytes lacuno-canalicular (OLC) system and paracrine signals such as sclerostin. Recently, our group reported abnormal ultrastructure of OLC system in AIS, which exhibiting shorter and fewer canaliculae, and larger roundish lacunae comparing with the controls. The upcoming research question is whether these structural changes are associated with abnormal osteocyte functions, including sclerostin expression in bone tissue and serum, and consequently bone mineralization and mechanical property? In this study, we hypothesized that ultrastructural changes of OLC system in AIS could be associated with abnormal osteocytic sclerostin expression, and manifested as impaired bone mineral homeostasis and mechanical property which might contribute to the initiation/progression of AIS.

Subjects and Methods: This is a case-control study. Iliac crest bone biopsies were taken intra-operatively from 5 AIS patients and 5 ethnic-and age-matched non-AIS controls under strict ethical approval. Basic anthropometric data, pubertal maturity and curve severity were measured. The fresh bone biopsies were examined by immunostaining, Energy Dispersive X-ray Spectrometry (EDX) and microindentation. The correlation of serum sclerostin (measured with Multiplex) and curve severity was obtained from an independent cohort study to determine the clinical implication of abnormal LCN ultrastructure and sclerostin expression.

Results: Immunostaining showed that AIS bone biopsies had lower number of sclerostin-positive osteocytes by 25.6% when compared with the controls (p<0.05), and a significant number of AIS osteocytes had sclerostin expression confined in their cell bodies, but not dispersed along the protruding dendrites (Fig. 1a), suggesting impaired sclerostin secretion. Linear regression analysis showed significant correlation between serum sclerostin
level and curve severity after adjustment with age (Fig. 1b). EDX results revealed that the calcium to phosphorous ratio, a representative marker of bone mineral status, was 4.6% lower (Fig. 1c), and microindentation study indicated lower Vickers hardness and less elastic modulus by 11.1 and 21.3%, respectively in the peri-osteocytic matrix of AIS (Fig. 1d).

Discussion and Conclusion: As a follow-up of previous ultrastructural study, we firstly demonstrated functional abnormality of osteocytes in AIS, including abnormally low sclerostin expression in dendritic processes, lower calcium to phosphorous ratio and reduced micro-hardness and elastic modulus of the peri-osteocytic matrix. We also observed a negative correlation of serum sclerostin with curve severity that might explain for the link of abnormal bone quality to the curve initiation/progression in AIS. The causes underlying abnormal OLC system may represent novel disgnostic/therapeutic targets for AIS.
All Author(s) ListW. Y. W. Lee, H. X. Chen, J. Zhang, Z. W. Wang, B. K. W. Ng, K. M. Lee, T. P. Lam, J. Q. Feng, J. C. Y. Cheng
Name of Conference2016 International Combined Meeting of Orthopaedics Research Societies
Start Date of Conference21/09/2016
End Date of Conference25/09/2016
Place of ConferenceXi'an, China
Country/Region of ConferenceChina
Year2016
LanguagesEnglish-United Kingdom

Last updated on 2018-22-01 at 09:17