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The Effect Of Parathyroid Hormone (1-34) On Lumbar Facet Joint Osteoarthritis In An Rat Model Induced By Collagenase (Type Ⅱ)

Posted on:2019-07-07Degree:MasterType:Thesis
Country:ChinaCandidate:Q L LvFull Text:PDF
GTID:2394330563490554Subject:Surgery
Abstract/Summary:PDF Full Text Request
Objectives The purpose of this study was to investigate the feasibility of intraarticular injection of type Ⅱ collagenase into male Sprague-Dawley(SD)rat lumbar facet joints to induce lumbar facet joint osteoarthritis(LFJOA).With the early administration of parathyroid hormone(PTH)in this LFJOA model,to explore the effect of PTH on articular cartilage,subchondral bone and pain in rats.Methods Thirty SPF grade 3-month-old male SD rats were randomly assigned into the sham group(n = 10),the collagenase(type Ⅱ)injection group(CⅡ group,n=10)and the PTH group(n = 10).CⅡ and PTH groups were operated and injected type Ⅱ collagenase into lumbar facet joints(LFJs)(right L3–L4,L4–L5,and L5–L6 FJs).Rats in the Sham group received the same surgical procedures as the collagenase injection rats,but collagenase was not injected into the FJs.Tactile allodynia test was performed before surgery(days 0)and on days 3,14,28 and 56 after surgery to measure the 50% paw withdrawal thresholds(PWT)of right hind of rats.PTH was given to the rats in the PTH group at the dose of 30ug/kg/1week by hypodermic injection,and the same volume of saline was given to the CⅡ group.All animals were sacrificed at the end point of 8 week of administration,then all lumbar vertebras were harvested and fixed in 4% formaldehyde for 72 h.After evaluated by Micro-CT,lumbar vertebras were decalcified for 12 weeks.Then all specimens were paraffin-embedded and sectioned to perform Toluidine blue staining and aggrecan(AGG),a disintegrin and metalloproteinase with thrombospondin motifs 4(ADAMTS-4)immunohistochemical staining.Toluidine blue staining sections were evaluated by modified Mankin histological score system to assess cartilage degeneration.The data of each group were collected for statistical analysis.Results 1 The Sham group displayed almost no degeneration of articular cartilage and the articular surface was smooth,the matrix was densely stained with toluidine blue.The CⅡ group presented a significantly degeneration,including reduced numbers of chondrocytes,surface fissures,and even denudation of the articular surface and higher modified Mankin score than the Sham group(P < 0.05).After administration of PTH,cartilage lesions of rats in the PTH group were significantly alleviated,the modified Mankin score was significantly dcreased as compared with that in CⅡ group(P < 0.05).2 Compared with Sham group,the expression of AGG in cartilage matrix in CⅡ group was significantly decreased(P < 0.05)and the expression of ADAMTS-4 was significantly increased(P < 0.05).In PTH group,the AGG expression level were significantly higher than that in the CⅡ group(P < 0.05),the ADAMTS-4 expression level were significantly lower than that in the CⅡ group(P < 0.05).There was no significant difference in the expression of AGG and ADAMTS-4 between PTH group and Sham group(P>0.05).3 Compared with Sham group,BMD,BV/TV and Tb.Th in CⅡ group were significantly decreased(P < 0.05).BMD,BV/TV and Tb.Th in PTH group were significantly higher than those in CⅡ group(P < 0.05).There was no significant difference in BMD,BV/TV and Tb.Th between PTH group and Sham group(P>0.05).4 The 50% paw withdrawal thresholds(PWT)in sham-operated rats did not display significantly change throughout the experiments.Both the CⅡ and PTH groups exhibited significantly lower 50% PWT values from day 3 postoperatively(P < 0.05).The 50% PWT in PTH group was significantly higher than that in the CⅡ group on day 3,14,28,56 after surgery(P < 0.05).Conclusions Intraarticular injection of collagenase(type Ⅱ)into LFJs could establish a rat model of LFJOA and result in the degeneration of articular cartilage,subchondral bone and hyperalgesia in rats.PTH intervention could alleviate cartilage damage,abnormal microstructural parameters of subchondral bone and relieve hyperalgesia to some extent in rats.
Keywords/Search Tags:parathyroid hormone (1-34), lumbar facet joint, osteoarthritis, pain, articular cartilage, subchondral bone
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