Development and characterization of supramolecular calcitonin assembly and assessment of its interactions with the bone remodelling process

Manglani, Kapil and Vijayan, Viji and Pathak, Chandramani and Khandelwal, Mayuri and Singh, Parminder and Chellappa, Stalin and Yadav, Vijay K and Surolia, Avadhesha and Gupta, Sarika (2019) Development and characterization of supramolecular calcitonin assembly and assessment of its interactions with the bone remodelling process. In: BONE, 122 . pp. 123-135.

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Abstract

Osteoporosis is the most common metabolic bone disease, which poses an immense socio-economic burden on the society. Human calcitonin, though safe, is not considered as a therapeutic option because of its high tendency to self-associate to form amyloid fibrils thereby affecting its potency. To circumvent this issue we harnessed the inherent capacity of aggregation and developed an assemblage of human calcitonin monomers, Supramolecular Calcitonin Assembly (SCA-I)], which releases biologically active calcitonin monomers in a sustained manner for a period of at least three weeks. AFM and FT-IR analysis showed that SCA-I is amorphous aggregates of calcitonin monomers. Both SCA-I and monomer released from it demonstrated superior anti-osteoclast activity and proteolytic stability in-vitro. SCA-I upon single injection significantly improved bone formation markers and reduced bone resorption markers in ovariectomized (OVX) rat model of postmenopausal osteoporosis. Micro-CT analysis revealed that calcitonin released from SCA-I exhibits its beneficial effect on cortical bone more profoundly compared to trabecular bone. This study demonstrates that SCA-I is more effective compared to the human calcitonin monomers on osteoclasts and has site-specific effect on bone in a model of post-menopausal osteoporosis. This approach opens up an innovative way to use and study the function of human calcitonin.

Item Type:	Journal Article
Publication:	BONE
Publisher:	ELSEVIER SCIENCE INC
Additional Information:	The copyright for this article belongs to Elsevier Inc.
Keywords:	Human calcitonin; Protein aggregation; Ovariectomy; Osteoporosis
Department/Centre:	Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited:	24 May 2019 09:19
Last Modified:	24 May 2019 09:19
URI:	http://eprints.iisc.ac.in/id/eprint/62653

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