Litsea glutinosa extract promotes fracture healing and prevents bone loss via BMP2/SMAD1 signaling

in Journal of Endocrinology
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Sonu Khanka Division of Endocrinology, CSIR-Central Drug Research Institute, Lucknow, India
Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, India

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Charul Somani Department of Chemistry, Mohanlal Sukhadia University, Udaipur-Rajasthan, India

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Kriti Sharma Division of Endocrinology, CSIR-Central Drug Research Institute, Lucknow, India
Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, India

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Shivani Sharma Division of Endocrinology, CSIR-Central Drug Research Institute, Lucknow, India
Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, India

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Akhilesh Kumar Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, India
Sophisticated Analytical Instrument Facility & Research, Division, CSIR-Central Drug Research Institute, Lucknow, India

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Naibedya Chattopadhyay Division of Endocrinology, CSIR-Central Drug Research Institute, Lucknow, India
Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, India

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Sanjeev K Kanojiya Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, India
Sophisticated Analytical Instrument Facility & Research, Division, CSIR-Central Drug Research Institute, Lucknow, India

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https://orcid.org/0000-0003-2473-0246
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Dinesh Kumar Yadav Department of Chemistry, Mohanlal Sukhadia University, Udaipur-Rajasthan, India

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Divya Singh Division of Endocrinology, CSIR-Central Drug Research Institute, Lucknow, India
Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, India

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https://orcid.org/0000-0002-2487-4082

Correspondence should be addressed to D K Yadav or D Singh: dineshkyadav@mlsu.ac.in or divya_singh@cdri.res.in
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Estrogen deficiency is one of the main causes for postmenopausal osteoporosis. Current osteoporotic therapies are of high cost and associated with serious side effects. So there is an urgent need for cost-effective anti-osteoporotic agents. Anti-osteoporotic activity of Litsea glutinosa extract (LGE) is less explored. Moreover, its role in fracture healing and mechanism of action is still unknown. In the present study we explore the osteoprotective potential of LGE in osteoblast cells and fractured and ovariectomized (Ovx) mice models. Alkaline phosphatase (ALP), MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and mineralization assays revealed that LGE treatment increased osteoblast cell differentiation, viability and mineralization. LGE treatment at 0.01 μg increased the expression of BMP2, PSMAD, RUNX2 and type 1 col. LGE also mitigated RANKL-induced osteoclastogenesis. Next, drill hole injury Balb/C mice model was treated with LGE for 12 days. Micro-CT analysis and Calcein labeling at the fracture site showed that LGE (20 mg/kg) enhanced new bone formation and bone regeneration, also increased expression of BMP2/SMAD1 signaling genes at fracture site. Ovx mice were treated with LGE for 1 month. μCT analysis indicated that the treatment of LGE at 20 mg/kg dose prevented the alteration in bone microarchitecture and maintained bone mineral density and bone mineral content. Treatment also increased bone strength and restored the bone turnover markers. Furthermore, in bone samples, LGE increased osteogenesis by enhancing the expression of BMP2/SMAD1 signaling components and decreased osteoclast number and surface. We conclude that LGE promotes osteogenesis via modulating the BMP2/SMAD1 signaling pathway. The study advocates the therapeutic potential of LGE in osteoporosis treatment.

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