Parathyroid hormone-(1-34) ameliorated knee osteoarthritis in rats via autophagy

Chung Hwan Chen, Mei Ling Ho, Ling Hua Chang, Lin Kang, Yi Shan Lin, Sung Yen Lin, Shun Cheng Wu, Je Ken Chang

Research output: Contribution to journalArticle

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Abstract

Anterior cruciate ligament (ACL) tear can lead to osteoarthritis (OA). However, parathyroid hormone (PTH)-(1-34) was found to alleviate OA progression in a papain-induced OA model. Autophagy is a protective mechanism in normal cartilage, and its aging-related loss is linked with chondrocyte death and OA. Thus we examined the roles of autophagy in PTH treatment in OA after ACL transection (ACLT). Thirty-six rats were randomized into three groups: control group, ACLT-induced OA (OA) group, and OA with intra-articular PTH-(1-34) treatment (OA+PTH) group. Weight-bearing and treadmill tests were evaluated. Cartilage matrix was determined by a histological evaluation of glycosaminoglycan (GAG), Osteoarthritis Research Society International (OARSI) score, chondrocyte apoptosis, and immunohistochemistry. Rats in the OA group had significantly decreased weight bearing and running endurance. The histological results indicated that GAG, collagen type II, and chondrocyte autophagy had decreased but that the OARSI score, terminal differentiation markers (collagen type X and Indian hedgehog), and chondrocyte apoptosis had increased in the OA group. Additionally, PTH-(1-34) treatment significantly improved weight bearing and treadmill endurance, preserved GAG and collagen type II, and reduced the OARSI score and terminal differentiation markers. Finally, PTH-(1-34) ameliorated chondrocyte apoptosis by regulating the expression of autophagy-related proteins, through reducing mechanistic target of rapamycin (mTOR) and p62 and enhancing microtubuleassociated protein-1 light chain 3 (LC3) and beclin-1. Reconstructive surgery after ACL rupture cannot prevent OA occurrence. Intraarticular PTH-(1-34) treatment can alleviate OA progression after ACLT and histological molecular changes. Possible mechanisms are reducing chondrocyte terminal differentiation and apoptosis, with increasing autophagy. NEW & NOTEWORTHY Anterior cruciate ligament (ACL) tear can lead to osteoarthritis (OA). Intra-articular parathyroid hormone (PTH)-(1-34) significantly improved weight bearing and treadmill endurance, preserved glycosaminoglycan and collagen type II, and reduced Osteoarthritis Research Society International (OARSI) score and terminal differentiation. Finally, PTH-(1-34) ameliorated chondrocyte apoptosis by regulating the expression of autophagy-related proteins, through reducing mechanistic target of rapamycin (mTOR) and p62 and enhancing microtubule-associated protein-1 light chain 3 (LC3) and beclin-1. PTH-(1-34) can alleviate OA progression after ACL transection. Possible mechanisms are reducing chondrocyte terminal differentiation and apoptosis, with increasing autophagy.

Original languageEnglish
Pages (from-to)1177-1185
Number of pages9
JournalJournal of Applied Physiology
Volume124
Issue number5
DOIs
Publication statusPublished - 2018 May 1

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Knee Osteoarthritis
Autophagy
Parathyroid Hormone
Osteoarthritis
Chondrocytes
Weight-Bearing
Apoptosis
Glycosaminoglycans
Collagen Type II
Anterior Cruciate Ligament
Differentiation Antigens
Sirolimus
Cartilage
Reconstructive Surgical Procedures
Joints
Collagen Type X
Light
Microtubule-Associated Proteins
Papain
Hedgehogs

All Science Journal Classification (ASJC) codes

  • Physiology
  • Physiology (medical)

Cite this

Chen, Chung Hwan ; Ho, Mei Ling ; Chang, Ling Hua ; Kang, Lin ; Lin, Yi Shan ; Lin, Sung Yen ; Wu, Shun Cheng ; Chang, Je Ken. / Parathyroid hormone-(1-34) ameliorated knee osteoarthritis in rats via autophagy. In: Journal of Applied Physiology. 2018 ; Vol. 124, No. 5. pp. 1177-1185.
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abstract = "Anterior cruciate ligament (ACL) tear can lead to osteoarthritis (OA). However, parathyroid hormone (PTH)-(1-34) was found to alleviate OA progression in a papain-induced OA model. Autophagy is a protective mechanism in normal cartilage, and its aging-related loss is linked with chondrocyte death and OA. Thus we examined the roles of autophagy in PTH treatment in OA after ACL transection (ACLT). Thirty-six rats were randomized into three groups: control group, ACLT-induced OA (OA) group, and OA with intra-articular PTH-(1-34) treatment (OA+PTH) group. Weight-bearing and treadmill tests were evaluated. Cartilage matrix was determined by a histological evaluation of glycosaminoglycan (GAG), Osteoarthritis Research Society International (OARSI) score, chondrocyte apoptosis, and immunohistochemistry. Rats in the OA group had significantly decreased weight bearing and running endurance. The histological results indicated that GAG, collagen type II, and chondrocyte autophagy had decreased but that the OARSI score, terminal differentiation markers (collagen type X and Indian hedgehog), and chondrocyte apoptosis had increased in the OA group. Additionally, PTH-(1-34) treatment significantly improved weight bearing and treadmill endurance, preserved GAG and collagen type II, and reduced the OARSI score and terminal differentiation markers. Finally, PTH-(1-34) ameliorated chondrocyte apoptosis by regulating the expression of autophagy-related proteins, through reducing mechanistic target of rapamycin (mTOR) and p62 and enhancing microtubuleassociated protein-1 light chain 3 (LC3) and beclin-1. Reconstructive surgery after ACL rupture cannot prevent OA occurrence. Intraarticular PTH-(1-34) treatment can alleviate OA progression after ACLT and histological molecular changes. Possible mechanisms are reducing chondrocyte terminal differentiation and apoptosis, with increasing autophagy. NEW & NOTEWORTHY Anterior cruciate ligament (ACL) tear can lead to osteoarthritis (OA). Intra-articular parathyroid hormone (PTH)-(1-34) significantly improved weight bearing and treadmill endurance, preserved glycosaminoglycan and collagen type II, and reduced Osteoarthritis Research Society International (OARSI) score and terminal differentiation. Finally, PTH-(1-34) ameliorated chondrocyte apoptosis by regulating the expression of autophagy-related proteins, through reducing mechanistic target of rapamycin (mTOR) and p62 and enhancing microtubule-associated protein-1 light chain 3 (LC3) and beclin-1. PTH-(1-34) can alleviate OA progression after ACL transection. Possible mechanisms are reducing chondrocyte terminal differentiation and apoptosis, with increasing autophagy.",
author = "Chen, {Chung Hwan} and Ho, {Mei Ling} and Chang, {Ling Hua} and Lin Kang and Lin, {Yi Shan} and Lin, {Sung Yen} and Wu, {Shun Cheng} and Chang, {Je Ken}",
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Chen, CH, Ho, ML, Chang, LH, Kang, L, Lin, YS, Lin, SY, Wu, SC & Chang, JK 2018, 'Parathyroid hormone-(1-34) ameliorated knee osteoarthritis in rats via autophagy', Journal of Applied Physiology, vol. 124, no. 5, pp. 1177-1185. https://doi.org/10.1152/japplphysiol.00871.2017

Parathyroid hormone-(1-34) ameliorated knee osteoarthritis in rats via autophagy. / Chen, Chung Hwan; Ho, Mei Ling; Chang, Ling Hua; Kang, Lin; Lin, Yi Shan; Lin, Sung Yen; Wu, Shun Cheng; Chang, Je Ken.

In: Journal of Applied Physiology, Vol. 124, No. 5, 01.05.2018, p. 1177-1185.

Research output: Contribution to journalArticle

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