Effect of intra-articular injection of a hyaluronic acid-alendronate conjugate on post-traumatic osteoarthritis induced by destabilization of the medial meniscus in rats.
Rats
Animals
Hyaluronic Acid
/ pharmacology
Alendronate
/ pharmacology
Menisci, Tibial
/ pathology
Sodium Chloride
/ pharmacology
X-Ray Microtomography
Vascular Endothelial Growth Factor A
/ pharmacology
Rats, Sprague-Dawley
Osteoarthritis
/ drug therapy
Injections, Intra-Articular
Cartilage, Articular
/ pathology
Disease Models, Animal
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
24 Nov 2023
24 Nov 2023
Historique:
received:
07
09
2023
accepted:
07
11
2023
medline:
27
11
2023
pubmed:
25
11
2023
entrez:
24
11
2023
Statut:
epublish
Résumé
Osteoarthritis (OA) is a chronic degenerative joint disease characterized by pain and cartilage damage. Intra-articular (i.a) viscosupplementation with hyaluronic acid (HA) is frequently used for the management of OA. Preclinical studies have reported that bisphosphonates (BPs) may have a therapeutic potential to slow down or reverse the progression of OA. Among these, alendronate (ALN) has demonstrated chondroprotective effects in both in vitro and vivo experiments. This study evaluated the effects of a novel alendronate-hyaluronic acid (ALN-HA) conjugate on an OA in vivo model induced by medial meniscus destabilization (DMM). DMM surgery was performed on the knees of Sprague Dawley rats that received, after four weeks, one intra-articular (i.a.) injection of: (1) ALN-HA; (2) HA; (3) sodium chloride (NaCl). Sham-operated rats were used as control. Allodynia was assessed by Von Frey test. Joint degeneration was evaluated eight weeks after treatment by micro-computed tomography (micro-CT), histology, and immunohistochemistry. Collagen cross-linked C-telopeptides (CTX-I and CTX-II) serum levels were determined by ELISA. Paw withdrawal threshold increased in ALN-HA group when compared to rats treated with NaCl or HA. Micro-CT did not show differences between ALN-HA, HA and NaCl groups. ALN-HA injection produced significant improvements in articular cartilage degeneration showing an OARSI score lower than those of HA and NaCl, and reduced matrix metalloproteinase (MMP)-13, MMP-3, interleukin-6, vascular endothelial growth factor and Caspase-3 expression. CTX-I was reduced after ALN-HA treatment when compared to NaCl. Our results indicate that i.a. use of ALN after conjugation with HA limits OA development and progression in the rat DMM model, and may lead to the development of novel therapeutic strategies in OA management.
Identifiants
pubmed: 38001135
doi: 10.1038/s41598-023-46965-5
pii: 10.1038/s41598-023-46965-5
pmc: PMC10673944
doi:
Substances chimiques
Hyaluronic Acid
9004-61-9
Alendronate
X1J18R4W8P
Sodium Chloride
451W47IQ8X
Vascular Endothelial Growth Factor A
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
20692Informations de copyright
© 2023. The Author(s).
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