PMID- 32638534
OWN - NLM
STAT- MEDLINE
DCOM- 20210104
LR  - 20210104
IS  - 2326-5205 (Electronic)
IS  - 2326-5191 (Linking)
VI  - 72
IP  - 12
DP  - 2020 Dec
TI  - The Role of the Non-neuronal Cholinergic System in Inflammation and Degradation 
      Processes in Osteoarthritis.
PG  - 2072-2082
LID - 10.1002/art.41429 [doi]
AB  - OBJECTIVE: The non-neuronal cholinergic system represents non-neuronal cells that 
      have the biochemical machinery to synthetize de novo and/or respond to 
      acetylcholine (ACh). We undertook this study to investigate this biochemical 
      machinery in chondrocytes and its involvement in osteoarthritis (OA). METHODS: 
      Expression of the biochemical machinery for ACh metabolism and nicotinic ACh 
      receptors (nAChR), particularly alpha7-nAChR, in human OA and murine chondrocytes was 
      determined by polymerase chain reaction and ligand-binding. We investigated the 
      messenger RNA expression of the human duplicate alpha7-nACh subunit, called CHRFAM7A, 
      which is responsible for truncated alpha7-nAChR. We assessed the effect of nAChR on 
      chondrocytes activated by interleukin-1beta (IL-1beta) and the involvement of alpha7-nAChR 
      using chondrocytes from wild-type (WT) and alpha7-deficient Chrna7(-/-) mice. The 
      role of alpha7-nAChR in OA was explored after medial meniscectomy in WT and 
      Chrna7(-/-) mice. RESULTS: Human and murine chondrocytes express the biochemical 
      partners of the non-neuronal cholinergic system and a functional alpha7-nAChR at 
      their cell surface (n = 5 experiments with 5 samples each). The expression of 
      CHRFAM7A in human OA chondrocytes (n = 23 samples) correlated positively with 
      matrix metalloproteinase 3 (MMP-3) (r = 0.38, P < 0.05) and MMP-13 (r = 0.48, P < 
      0.05) expression. Nicotine decreased the IL-1beta-induced IL-6 and MMP expression, 
      in a dose-dependent manner, in WT chondrocytes but not in Chrna7(-/-) 
      chondrocytes. Chrna7(-/-) mice that underwent meniscectomy (n = 7) displayed more 
      severe OA cartilage damage (mean +/- SD Osteoarthritis Research Society 
      International [OARSI] score 4.46 +/- 1.09) compared to WT mice that underwent 
      meniscectomy (n = 9) (mean +/- SD OARSI score 3.05 +/- 0.9; P < 0.05). CONCLUSION: 
      The non-neuronal cholinergic system is functionally expressed in chondrocytes. 
      Stimulation of nAChR induces antiinflammatory and anticatabolic activity through 
      alpha7-nAChR, but the anticatabolic activity may be mitigated by truncated alpha7-nAChR 
      in human chondrocytes. In vivo experiments strongly suggest that alpha7-nAChR has a 
      protective role in OA.
CI  - (c) 2020, American College of Rheumatology.
FAU - Courties, Alice
AU  - Courties A
AUID- ORCID: 0000-0001-8122-701X
AD  - Sorbonne Universite, INSERM UMR 938, Centre de Recherche Saint-Antoine, Hopital 
      Saint-Antoine, AP-HP, Paris, France.
FAU - Do, Ariane
AU  - Do A
AD  - Sorbonne Universite, INSERM UMR 938, Centre de Recherche Saint-Antoine, Hopital 
      Saint-Antoine, AP-HP, Paris, France.
FAU - Leite, Sarah
AU  - Leite S
AD  - Sorbonne Universite, INSERM UMR 938, Centre de Recherche Saint-Antoine, Hopital 
      Saint-Antoine, AP-HP, Paris, France.
FAU - Legris, Manon
AU  - Legris M
AD  - Sorbonne Universite, INSERM UMR 938, Centre de Recherche Saint-Antoine, Hopital 
      Saint-Antoine, AP-HP, Paris, France.
FAU - Sudre, Laure
AU  - Sudre L
AD  - Sorbonne Universite, INSERM UMR 938, Centre de Recherche Saint-Antoine, Hopital 
      Saint-Antoine, AP-HP, Paris, France.
FAU - Pigenet, Audrey
AU  - Pigenet A
AD  - Sorbonne Universite, INSERM UMR 938, Centre de Recherche Saint-Antoine, Hopital 
      Saint-Antoine, AP-HP, Paris, France.
FAU - Petit, Juliette
AU  - Petit J
AD  - Sorbonne Universite, INSERM UMR 938, Centre de Recherche Saint-Antoine, Hopital 
      Saint-Antoine, AP-HP, Paris, France.
FAU - Nourissat, Geoffroy
AU  - Nourissat G
AD  - 2INSERM UMR 938, Centre de Recherche Saint-Antoine, Clinique Maussins, Groupe 
      Ramsay Generale de Sante, Paris, France.
FAU - Cambon-Binder, Adeline
AU  - Cambon-Binder A
AD  - Sorbonne Universite, INSERM UMR 938, Centre de Recherche Saint-Antoine, Hopital 
      Saint-Antoine, AP-HP, Paris, France.
FAU - Maskos, Uwe
AU  - Maskos U
AD  - Institut Pasteur, Neurobiologie Integrative des Systemes Cholinergiques, CNRS UMR 
      3571, Paris, France.
FAU - Berenbaum, Francis
AU  - Berenbaum F
AD  - Sorbonne Universite, INSERM UMR 938, Centre de Recherche Saint-Antoine, Hopital 
      Saint-Antoine, AP-HP, Paris, France.
FAU - Sellam, Jeremie
AU  - Sellam J
AD  - Sorbonne Universite, INSERM UMR 938, Centre de Recherche Saint-Antoine, Hopital 
      Saint-Antoine, AP-HP, Paris, France.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20201025
PL  - United States
TA  - Arthritis Rheumatol
JT  - Arthritis & rheumatology (Hoboken, N.J.)
JID - 101623795
RN  - 0 (Receptors, Nicotinic)
RN  - 0 (alpha7 Nicotinic Acetylcholine Receptor)
RN  - EC 1.14.15.6 (Cholesterol Side-Chain Cleavage Enzyme)
SB  - IM
MH  - Aged
MH  - Animals
MH  - Cholesterol Side-Chain Cleavage Enzyme/metabolism
MH  - Chondrocytes/*metabolism
MH  - Female
MH  - Humans
MH  - Inflammation/*metabolism
MH  - Male
MH  - Mice
MH  - Middle Aged
MH  - Non-Neuronal Cholinergic System/*physiology
MH  - Osteoarthritis/*metabolism
MH  - Receptors, Nicotinic/*metabolism
MH  - alpha7 Nicotinic Acetylcholine Receptor/metabolism
EDAT- 2020/07/09 06:00
MHDA- 2021/01/05 06:00
CRDT- 2020/07/09 06:00
PHST- 2019/09/24 00:00 [received]
PHST- 2020/06/27 00:00 [accepted]
PHST- 2020/07/09 06:00 [pubmed]
PHST- 2021/01/05 06:00 [medline]
PHST- 2020/07/09 06:00 [entrez]
AID - 10.1002/art.41429 [doi]
PST - ppublish
SO  - Arthritis Rheumatol. 2020 Dec;72(12):2072-2082. doi: 10.1002/art.41429. Epub 2020 
      Oct 25.