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J Orthop Surg Res. 2019 Jun 13;14(1):177. doi: 10.1186/s13018-019-1210-1.

Combined low-dose LiCl and LY294002 for the treatment of osteoporosis in ovariectomized rats.

Author information

1
Department of Ophthalmology, Taizhou Central Hospital (Taizhou University Hospital), 999 Donghaidadao St, Jiaojiang District, Taizhou, 318000, Zhejiang Province, China.
2
The Fourth Affiliated Hospital of Nanchang University, 133 Guangchangnan St., Xihu District, Nanchang, China.
3
School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin, China.
4
The Fourth Affiliated Hospital of Nanchang University, 133 Guangchangnan St., Xihu District, Nanchang, China. jianhaibai@163.com.

Abstract

BACKGROUND:

To provide a low-toxicity and high-efficacy clinical treatment for osteoporosis via a novel combination of LiCl and LY294002.

METHODS:

The protein levels of p-AKT, AKT, p-GSK3β, GSK3β, β-catenin, p-β-catenin, and NFATC1 were measured in osteoblasts and osteoclasts by Western blot. ALP activity and TRACP activity were measured using the corresponding kit. The levels of BALP, PINP, CTX, and TRACP-5b were determined in accordance with the requirements of the ELISA kits. Microstructural analysis was performed on the left distal femur using microcomputed tomography.

RESULTS:

Treatment with the combination of LiCl and LY294002 led to a markedly increased osteoblast activity but significantly decreased osteoclast differentiation and bone absorption capacity compared with the treatment with LiCl or LY294002 alone (P < 0.01). In serum, the low-dose combination of LiCl and LY294002 significantly enhanced BALP levels (P < 0.01) and significantly decreased PINP, TRACP-5b, and CTX levels (P < 0.01) compared with the application of either drug alone.

CONCLUSIONS:

This study indicates that drug combinations directed at multiple targets could be used for osteoporosis treatment by promoting osteoblast proliferation and inhibiting differentiation with high efficiency.

KEYWORDS:

LY294002; Lithium chloride; NFATC1; Osteoblasts; Osteoporosis

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