局部应用甲状旁腺激素通过PKA/TRPV4通路协同正畸力加速大鼠牙移动的作用

doi:10.3969/j.issn.1006-5725.2026.14.012

Abstract

Abstract:

Objective To investigate whether the local application of parathyroid hormone （PTH） can activate the protein kinase A （PKA）/transient receptor potential vanilloid 4 （TRPV4） pathway to synergistically accelerate orthodontic tooth movement in rats and to explore its mechanism of action. Methods Forty-eight male Sprague-Dawley （SD） rats were randomly divided into four groups： a blank control group， a pure orthodontic tooth movement （OTM） group， a pure PTH administration group （PTH group）， and a combined orthodontic tooth movement and PTH administration group （OTM + PTH group）. A left maxillary first molar orthodontic movement model was established in the rats. A constant traction force of 0.6 N was applied， and the corresponding drugs were injected locally every other day. On the 10th day after model establishment， the tooth movement distance， the bone density on the pressure side， the periodontal histopathological changes， and the expression levels of PKA， TRPV4， and the ratio of receptor activator of nuclear factor-κB ligand （RANKL） to osteoprotegerin （OPG） were measured. RAW264.7 cells were cultured in vitro and induced to differentiate into osteoclasts with 50 ng/mL RANKL. Subsequently， PTH and PKA/TRPV4 pathway agonists or inhibitors were added， and the expression of relevant molecules was detected. Results Compared with the OTM group， the tooth movement distance in the OTM + PTH group was significantly greater. The bone density on the pressure side decreased， the number of osteoclasts increased， and the levels of PKA， TRPV4， and the RANKL/OPG ratio were significantly upregulated （P < 0.05）. In vitro experiments demonstrated that PKA or TRPV4 agonists could enhance the osteoclast-differentiation-promoting effect of PTH， whereas inhibitors could significantly impede this effect. Conclusions Local PTH treatment activates the PKA/TRPV4 signaling pathway， increases the RANKL/OPG ratio， and acts synergistically with orthodontic forces to promote osteoclast differentiation and activation. This enhances the efficiency of alveolar bone remodeling and consequently accelerates orthodontic tooth movement. This study offers a new theoretical foundation for optimizing clinical orthodontic treatment protocols.

Key words: parathyroid hormone, orthodontic tooth movement, protein kinase A, TRPV4, bone remodeling, osteoclast

CLC Number:

R783

Yimin RAN,Youli CHEN,Xi ZENG,Zhenglong TANG. Study on the effect of local application of parathyroid hormone accelerating tooth movement in rats through PKA/TRPV4 pathway in synergy with orthodontic force[J]. The Journal of Practical Medicine, 2026, 42(14): 2588-2602.

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引物名称	引物序列（5′→3′）
TRPV4	F：GCACGCCACCCTACCCTTACC
TRPV4	R：CGCAGACACAACCACCAGCACT
OPG	F：CTCCTGGTGTTCTTGGACATCATTG
OPG	R：GAGTAGTCAGGGCAAGGGACACAC
RANKL	F：CACACCAAGGGACGACGGAATC
RANKL	R：GGCAGCCACCACTACCACAGAGA
PKA	F：TTCAGGTGACAGACTTCGGTTTTG
PKA	R：TTGTTGTAGCCTTTGCTCAGGATAAT
GAPDH	F：TTCAGCTCTGGGATGACCTT
GAPDH	R：TGCCACTCAGAAGACTGTGG

引物名称	引物序列（5′→3′）
TRPV4	F：GCACGCCACCCTACCCTTACC
TRPV4	R：CGCAGACACAACCACCAGCACT
OPG	F：CTCCTGGTGTTCTTGGACATCATTG
OPG	R：GAGTAGTCAGGGCAAGGGACACAC
RANKL	F：CACACCAAGGGACGACGGAATC
RANKL	R：GGCAGCCACCACTACCACAGAGA
PKA	F：CTAAAGCAGATCGAGCACACTC
PKA	R：GCCACCAGCTACATACTCCA
GAPDH	F：TTCAGCTCTGGGATGACCTT
GAPDH	R：TGCCACTCAGAAGACTGTGG

组别	OTM距离
PTH组	0.03 ± 0.02
OTM组	0.29 ± 0.02 ^#
OTM+PTH组	0.46 ± 0.08 ^#&
P值	< 0.001
F值	106.8

组别	BV/TV/%	BMD/（mg/cm³）
PTH组	0.47 ± 0.03	533.59 ± 17.74
OTM组	0.38 ± 0.02^#	387.63 ± 13.30^#
OTM+PTH组	0.27 ± 0.05^#&	331.40 ± 15.20^#&
P值	0.001	< 0.001
F值	25.07	135.6

组别	TRPV4	PKA
Control组	1.00 ± 0.01	1.01 ± 0.01
PTH组	1.33 ± 0.08 ^*	2.18 ± 0.09 ^*
OTM组	1.77 ± 0.11 *^#**	1.07 ± 0.11 *^#**
OTM+PTH组	2.33 ± 0.16 *^#&**	3.32 ± 0.26 *^#&**
P值	< 0.001	< 0.001
F值	91.02	169.4

Study on the effect of local application of parathyroid hormone accelerating tooth movement in rats through PKA/TRPV4 pathway in synergy with orthodontic force

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组别	TRPV4	p-PKA/PKA
Control组	0.63 ± 0.08	0.48 ± 0.01
PTH组	0.69 ± 0.04	0.98 ± 0.02 ^*
OTM组	0.84 ± 0.03 *^#**	0.83 ± 0.06 *^#**
OTM+PTH组	0.97 ± 0.04 *^#&**	1.11 ± 0.02 *^#&**
P值	< 0.001	< 0.001
F值	27.03	215.3

组别	RANKL/ OPG蛋白比值	RANKL/ OPG mRNA比值
Control组	0.06 ± 0.02	1.01 ± 0.01
PTH组	0.69 ± 0.06	1.13 ± 0.25
OTM组	0.90 ± 0.04 *^#**	3.54 ± 0.19 *^#**
OTM+PTH组	1.04 ± 0.03^*#&	7.32 ± 1.21 *^#&**
P值	< 0.001	< 0.001
F值	72.30	333.3

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