Current knowledge of pituitary adenylate cyclase activating polypeptide (PACAP) in articular cartilage.
Animals
Antirheumatic Agents
/ therapeutic use
Cartilage, Articular
/ drug effects
Chondrocytes
/ drug effects
Chondrogenesis
/ drug effects
Humans
Osteoarthritis
/ drug therapy
Pituitary Adenylate Cyclase-Activating Polypeptide
/ metabolism
Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide
/ metabolism
Signal Transduction
Journal
Histology and histopathology
ISSN: 1699-5848
Titre abrégé: Histol Histopathol
Pays: Spain
ID NLM: 8609357
Informations de publication
Date de publication:
Nov 2020
Nov 2020
Historique:
pubmed:
17
6
2020
medline:
14
10
2021
entrez:
17
6
2020
Statut:
ppublish
Résumé
Pituitary adenylate cyclase activating polypeptide (PACAP) is an evolutionally well conserved neuropeptide, mainly expressed by neuronal and peripheral cells. It proves to be an interesting object of study both for its trophic functions during the development of several tissues and for its protective effects against oxidative stress, hypoxia, inflammation and apoptosis in different degenerative diseases. This brief review summarises the recent findings concerning the role of PACAP in the articular cartilage. PACAP and its receptors are expressed during chondrogenesis and are shown to activate the pathways involved in regulating cartilage development. Moreover, this neuropeptide proves to be chondroprotective against those stressors that determine cartilage degeneration and contribute to the onset of osteoarthritis (OA), the most common form of degenerative joint disease. Indeed, the degenerated cartilage exhibits low levels of PACAP, suggesting that its endogenous levels in adult cartilage may play an essential role in maintaining physiological properties. Thanks to its peculiar characteristics, exogenous administration of PACAP could be suggested as a potential tool to slow down the progression of OA and for cartilage regeneration approaches.
Identifiants
pubmed: 32542641
pii: HH-18-233
doi: 10.14670/HH-18-233
doi:
Substances chimiques
Antirheumatic Agents
0
Pituitary Adenylate Cyclase-Activating Polypeptide
0
Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide
0
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
1251-1262Subventions
Organisme : -
ID : -
Références
Aigner T. and Stöve J. (2003). Collagens-major component of the physiological cartilage matrix, major target of cartilage degeneration, major tool in cartilage repair. Adv. Drug. Deliv. Rev. 28, 55, 1569- 1593.
pubmed: 14623402
Alsalameh S., Amin R., Gemba T. and Lotz M. (2004). Identification of mesenchymal progenitor cells in normal and osteoarthritic human articular cartilage. Arthritis Rheum. 50, 1522-1532.
pubmed: 15146422
Blewis M.E., Nugent-Derfus G.E., Schmidt T.A., Schumacher B.L. and Sah R.L. (2007). A model of synovial fluid lubricant composition in normal and injured joints. Eur. Cell Mater. 6, 26-39.
pubmed: 17340555
Brubel R., Reglodi D., Jambor E., Koppan M., Varnagy A., Biro Z., Kiss P., Gaal V., Matkovits A., Farkas J., Lubics A., Bodis J., Bay C., Veszpremi B., Tamas A., Nemeth J. and Mark L. (2011). Investigation of pituitary adenylate cyclase activating polypeptide in human gynecological and other biological fluids by using MALDI TOF mass spectrometry. J. Mass. Spectrom. 46, 189-194.
pubmed: 21259400
Cameron D.B., Galas L., Jiang Y., Raoult E, Vaudry D. and Komuro H. (2007). Cerebellar cortical-layer-specific control of neuronal migration by pituitary adenylate cyclase-activating polypeptide. Neuroscience 146, 697-712.
pmcid: PMC1951536
pubmed: 17383102
Carballo C.B., Nakagawa Y., Sekiya I. and Rodeo S.A. (2017). Basic science of articular cartilage. Clin. Sports Med. 36, 413-425.
pubmed: 28577703
Castrogiovanni P., Di Rosa M., Ravalli S., Castorina A., Guglielmino C., Imbesi R., Vecchio M., Drago F., Szychlinska M.A. and Musumeci G. (2019). Moderate physical activity as a prevention method for knee osteoarthritis and the role of synoviocytes as biological key. Int. J. Mol. Sci. 20, E511.
pmcid: PMC6387266
pubmed: 30691048
Csanaky K., Reglődi D., Bánki E., Tarcai I., Márk L., Helyes Z., Ertl T., Gyarmati J., Horváth K., Sántik L. and Tamás A. (2013). Examination of PACAP38-like immunoreactivity in different milk and infant formula samples. Acta Physiol. Hung.100, 28-36.
pubmed: 23471040
Delgado M., Abad C., Martinez C., Juarranz M.G., Leceta J., Ganea D. and Gomariz R.P. (2003). PACAP in immunity and inflammation. Ann. N. Y. Acad. Sci. 992, 141-157.
pubmed: 12794054
Demoor M., Ollitrault D., Gomez-Leduc T., Bouyoucef M., Hervieu M., Fabre H., Lafont J., Denoix J.M., Audigié F., Mallein-Gerin F., Legendre F. and Galera P. (2014). Cartilage tissue engineering: molecular control of chondrocyte differentiation for proper cartilage matrix reconstruction. Biochim. Biophys. Acta 1840, 2414-2440.
pubmed: 24608030
Di Rosa M., Szychlinska M.A., Tibullo D., Malaguarnera L. and Musumeci G. Expression of CHI3L1 and CHIT1 in osteoarthritic rat cartilage model. A morphological study. (2014). Eur. J. Histochem. 58, 2423.
pmcid: PMC4194398
pubmed: 25308850
Douiri S., Bahdoudi S., Hamdi Y., Cubì R., Basille M., Fournier A., Vaudry H., Tonon M.C., Amri M., Vaudry D. and Masmoudi-Kouki O. (2016a). Involvement of endogenous antioxidant systems in the protective activity of pituitary adenylate cyclase-activating polypeptide against hydrogen peroxide-induced oxidative damages in cultured rat astrocytes. J. Neurochem. 137, 913-930.
pubmed: 26991551
Fermor B., Christensen S.E., Youn I., Cernanec J.M., Davies C.M. and Weinberg J.B. (2007). Oxygen, nitric oxide and articular cartilage. Eur. Cell Mater. 13, 56-65.
pubmed: 17427142
Fonsi M., El Amrani A.I., Gervais F. and Vincent P. (2019). Intraarticular hyaluronic acid and chondroitin sulfate: Pharmacokinetic investigation in osteoarthritic rat models. Curr. Ther. Res. Clin. Exp. 92, 100573.
pmcid: PMC6957868
pubmed: 31956378
Gaytan F., Martinez-Fuentes A.J., Garcia-Navarro F., Vaudry H. and Aguilar E. (1994). Pituitary adenylate cyclase-activating peptide (PACAP) immunolocalization in lymphoid tissues of the rat. Cell Tissue Res. 276, 223-227.
pubmed: 8020059
Giunta S., Castorina A., Marzagalli R., Szychlinska M.A., Pichler K., Mobasheri A. and Musumeci G. (2015). Ameliorative effects of PACAP against cartilage degeneration. Morphological, immunohistochemical and biochemical evidence from in vivo and in vitro models of rat osteoarthritis. Int. J. Mol. Sci. 16, 5922-5944.
pmcid: PMC4394513
pubmed: 25782157
Gonzalez B.J., Basille M., Vaudry D., Fournier A. and Vaudry H. (1997). Pituitary adenylate cyclase-activating polypeptide promotes cell survival and neurite outgrowth in rat cerebellar neuroblasts. Neuroscience 78, 419-430.
pubmed: 9145799
Hauser-Kronberger C., Hacker G.W., Albegger K., Muss W.H., Sundler F., Arimura A. and Dietze O. (1996). Distribution of two VIP-related peptides, helospectin and pituitary adenylate cyclase activating peptide (PACAP), in the human upper respiratory system. Regul. Pept. 65, 203-209.
pubmed: 8897643
Horvath G., Opper B. and Reglodi D. (2019). The neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) is protective in inflammation and oxidative stress-induced damage in the kidney. Int. J. Mol. Sci. 20, 4944.
pmcid: PMC6801442
pubmed: 31591326
Johnstone B., Alini M., Cucchiarini M., Dodge G.R., Eglin D., Guilak F., Madry H., Mata A., Mauck R.L., Semino C.E. and Stoddart M.J. (2013). Tissue engineering for articular cartilage repair--the state of the art. Eur. Cell Mater. 25, 248-267.
pubmed: 23636950
Jolivel V., Basille M., Aubert N., de Jouffrey S., Ancian P., Le Bigot J.F., Noack P., Massonneau M., Fournier A., Vaudry H., Gonzalez B.J. and Vaudry D. (2009). Distribution and functional characterization of pituitary adenylate cyclase-activating polypeptide receptors in the brain of non-human primates. Neuroscience 160, 434-451
pubmed: 19236905
Józsa G., Szegeczki V., Pálfi A., Kiss T., Helyes Z., Fülöp B., Cserháti C., Daróczi L., Tamás A., Zákány R., Reglődi D. and Juhász T. (2018). Signalling alterations in bones of pituitary adenylate cyclase activating polypeptide (PACAP) gene deficient mice. Int. J. Mol. Sci. 19, 2538.
pmcid: PMC6163297
pubmed: 30150589
Juhász T ., Matta C., Katona É., Somogyi C., T akács R., Gergely P ., Csernoch L., Panyi G., Tóth G., Reglődi D., Tamás A. and Zákány R. (2014a). Pituitary adenylate cyclase activating polypeptide (PACAP) signalling exerts chondrogenesis promoting and protecting effects: implication of calcineurin as a downstream target. PLoS One 9, e91541.
pmcid: PMC3958376
pubmed: 24643018
Juhász T ., Matta C., Somogyi C., Katona É., T akács R., Soha R.F ., Szabó I.A., Cserháti C., Sződy R., Karácsonyi Z., Bakó E., Gergely P. and Zákány R. (2014b). Mechanical loading stimulates chondrogenesis via the PKA/CREB-Sox9 and PP2A pathways in chicken micromass cultures. Cell Signal. 26, 468-482.
pubmed: 24333667
Juhász T., Matta C., Katona É., Somogyi C., Takács R., Hajdú T., Helgadottir S.L., Fodor J., Csernoch L., Tóth G., Bakó É., Reglődi D., Tamás A. and Zákány R. (2014c). Pituitary adenylate cyclase-activating polypeptide (PACAP) signalling enhances osteogenesis in UMR-106 cell line. J. Mol. Neurosci. 54, 555-573.
pubmed: 25112418
Juhász T., Helgadottir S.L., Tamás A., Reglődi D. and Zákány R. (2015a). PACAP and VIP signaling in chondrogenesis and osteogenesis. Peptides 66, 51-57.
pubmed: 25701761
Juhász T., Szentléleky E., Somogyi C.S., Takács R., Dobrosi N., Engler M., Tamás A., Reglődi D. and Zákány R. (2015b). Pituitary adenylate cyclase activating polypeptide (PACAP) pathway is induced by mechanical load and reduces the activity of hedgehog signaling in chondrogenic micromass cell cultures. Int. J. Mol. Sci. 16, 17344-17367.
pmcid: PMC4581197
pubmed: 26230691
Kang R.W., Friel N.A., Williams J.M., Cole B.J. and Wimmer M.A. (2010). Effect of impaction sequence on osteochondral graft damage: the role of repeated and varying loads. Am. J. Sports Med. 38, 105-113.
pmcid: PMC3827775
pubmed: 19915099
Kano M., Shimizu Y., Suzuki Y., Furukawa Y., Ishida H., Oikawa M., Kanetaka H., Ichikawa H. and Suzuki T. (2011). Pituitary adenylate cyclase activating polypeptide-immunoreactive nerve fibers in the rat epiglottis and pharynx. Ann. Anat. 193, 494-499.
pubmed: 21955674
Karimi T., Barati D., Karaman O., Moeinzadeh S. and Jabbari E. (2015). A developmentally inspired combined mechanical and biochemical signaling approach on zonal lineage commitment of mesenchymal stem cells in articular cartilage regeneration. Integr. Biol. (Camb). 7, 112-127.
pmcid: PMC4275337
pubmed: 25387395
Lefebvre V. (2019). Roles and regulation of SOX transcription factors in skeletogenesis. Curr. Top Dev. Biol. 133, 171-193
pmcid: PMC6955022
pubmed: 30902252
Lepetsos P. and Papavassiliou A.G. (2016). ROS/oxidative stress signaling in osteoarthritis. Biochim. Biophys. Acta 1862, 576-591.
pubmed: 26769361
Lieberthal J., Sambamurthy N. and Scanzello C.R. (2015). Inflammation in joint injury and post-traumatic osteoarthritis. Osteoarthritis Cartilage 23, 1825-1834.
pmcid: PMC4630675
pubmed: 26521728
Loeser R.F. (2010). Age-related changes in the musculoskeletal system and the development of osteoarthritis. Clin. Geriatr. Med. 26, 371- 386.
pmcid: PMC2920876
pubmed: 20699160
Loreto C., Musumeci G. and Leonardi R. (2009). Chondrocyte-like apoptosis in temporomandibular joint disc internal derangement as a repair-limiting mechanism. An in vivo study. Histol. Histopathol. 24, 293-298.
pubmed: 19130398
Maduna T. and Lelievre V. (2016). Neuropeptides shaping the central nervous system development: Spatiotemporal actions of VIP and PACAP through complementary signaling pathways. J. Neurosci. Res. 94, 1472-1487.
pubmed: 27717098
Matta C., Mobasheri A., Gergely P. and Zákány R. (2014). Ser/Thrphosphoprotein phosphatases in chondrogenesis: neglected components of a two-player game. Cell Signal. 262175-2185.
pubmed: 25007994
Maugeri G., Longo A., D'Amico A.G., Rasà D.M., Reibaldi M., Russo A., Bonfiglio V., Avitabile T. and D'Agata V. (2018a). Trophic effect of PACAP on human corneal endothelium. Peptides 99, 20-26.
pubmed: 29126993
Maugeri G., D'Amico A.G., Rasà D.M., Saccone S., Federico C., Cavallaro S. and D'Agata V. (2018b) PACAP and VIP regulate hypoxia-inducible factors in neuroblastoma cells exposed to hypoxia. Neuropeptides 69, 84-91.
pubmed: 29699729
Maugeri G., D'Amico A.G., Bucolo C. and D'Agata V. (2019a). Protective effect of PACAP-38 on retinal pigmented epithelium in an in vitro and in vivo model of diabetic retinopathy through EGFRdependent mechanism. Peptides 119, 170108.
pubmed: 31247223
Maugeri G., D'Amico A.G., Rasà D.M., Federico C., Saccone S., Morello G., La Cognata V., Cavallaro S. and D'Agata V. (2019b). Molecular mechanisms involved in the protective effect of pituitary adenylate cyclase-activating polypeptide in an in vitro model of amyotrophic lateral sclerosis. J. Cell. Physiol. 234, 5203-5214.
pubmed: 30238989
Mehana E.E., Khafaga A.F. and El-Blehi S.S. (2019). The role of matrix metalloproteinases in osteoarthritis pathogenesis: An updated review. Life Sci. 234,116786.
pubmed: 31445934
Miyata A., Arimura A., Dahl R.R., Minamino N., Uehara A., Jiang L, Culler M.D. and Coy D.H. (1989). Isolation of a novel 38 residuehypothalamic polypeptide which stimulates adenylate cyclase in pituitary cells. Biochem. Biophys Res. Commun. 164, 567-574.
pubmed: 2803320
Miyata A., Jiang L., Dahl R.D., Kitada C., Kubo K., Fujino M., Minamino N. and Arimura A. (1990). Isolation of a neuropeptide corresponding to the N-terminal 27 residues of the pituitary adenylate cyclase activating polypeptide with 38 residues (PACAP38). Biochem. Biophys. Res. Commun. 170, 643-648.
pubmed: 2383262
Mobasheri A., Matta C., Zákány R. and Musumeci G. (2015). Chondrosenescence: definition, hallmarks and potential role in the pathogenesis of osteoarthritis. Maturitas 80, 237-244
pubmed: 25637957
Musumeci G., Castrogiovanni P., Trovato F.M., Imbesi R., Giunta S., Szychlinska M.A., Loreto C., Castorina S. and Mobasheri A. (2015). Physical activity ameliorates cartilage degeneration in a rat model of aging: a study on lubricin expression. Scand. J. Med. Sci. Sports. 25, e222-30.
pubmed: 25039883
Nakamura K., Nakamachi T., Endo K., Ito K., Machida T., Oka T., Hori M., Ishizaka K. and Shioda S. (2014). Distribution of pituitary adenylate cyclase-activating polypeptide (PACAP) in the human testis and in testicular germ cell tumors. Andrologia 46, 465-471.
pubmed: 23621806
Nemirov D., Nakagawa Y., Sun Z., Lebaschi A., Wada S., Carballo C., Deng X.H., Putnam D., Bonassar L.J. and Rodeo S.A. (2020). Effect of lubricin mimetics on the inhibition of osteoarthritis in a rat anterior cruciate ligament transection model. Am. J. Sports Med. 48, 624- 634.
pubmed: 32004084
Newman A.P. and Articular cartilage repair (1998). Am. J. Sports Med. 26, 309-324.
pubmed: 9548130
Niewiadomski P., Zhujiang A., Youssef M. and Waschek J.A. (2013). Interaction of PACAP with Sonic hedgehog reveals complex regulation of the hedgehog pathway by PKA. Cell Signal. 25, 2222-2230.
pmcid: PMC3768265
pubmed: 23872071
Piera-Velazquez S., Hawkins D.F., Whitecavage M.K., Colter D.C., Stokes D.G. and Jimenez S.A. (2007). Regulation of the human SOX9 promoter by Sp1 and CREB. Exp. Cell Res. 313, 1069-1079.
pmcid: PMC2118054
pubmed: 17289023
Pirone A., Baoan D., Piano I., Della Santina L., Baglini A. and Lenzi C. (2011). Pituitary adenylate cyclase-activating peptide (PACAP) immunoreactivity distribution in the small intestine of the adult New Hampshire chicken. Acta Histochem. 113, 477-483
pubmed: 20598353
Poole A.R., Kojima T., Yasuda T., Mwale F., Kobayashi M. and Laverty S. (2001). Composition and structure of articular cartilage: a template for tissue repair. Clin. Orthop. Relat. Res. 26-33.
pubmed: 11603710
Rahmati M., Nalesso G., Mobasheri A. and Mozafari M. (2017). Aging and osteoarthritis: Central role of the extracellular matrix. Ageing Res. Rev. 40, 20-30.
pubmed: 28774716
Rai M.F., Stoddart M.J. and Guilak F. (2017). Mechanical signals as regulators of cartilage degeneration and regeneration. J. Am. Acad. Orthop. Surg. 25, 87-89.
pubmed: 28291148
Ratneswaran A., Rockel J.S. and Kapoor M. (2020). Understanding osteoarthritis pathogenesis: a multiomics system-based approach. Curr. Opin. Rheumatol. 32, 80-91.
pubmed: 31724972
Ravalli S., Szychlinska M.A., Lauretta G., Di Rosa M. and Musumeci G. (2020). Investigating lubricin and known cartilage-based biomarkers of osteoarthritis. Expert Rev. Mol. Diagn. 1-10.
pubmed: 32085680
Redman N., Oldfield S.F. and Archer C.W. (2005). Current strategies for articular cartilage repair. Eur. Cell Mater. 9, 23-32.
pubmed: 15830323
Reglodi D., Atlasz T., Szabo E., Jungling A., Tamas A., Juhasz T., Fulop B.D. and Bardosi A. (2018a). PACAP deficiency as a model of aging. Geroscience 40, 437-452.
pmcid: PMC6294727
pubmed: 30345481
Reglodi D., Cseh S., Somoskoi B., Fulop B.D., Szentleleky E., Szegeczki V., Kovacs A., Varga A., Kiss P., Hashimoto H., Tamas A., Bardosi A., Manavalan S., Bako E., Zakany R. and Juhasz T. (2018b). Disturbed spermatogenic signaling in pituitary adenylate cyclase activating polypeptide-deficient mice. Reproduction 155, 129-139.
pubmed: 29101268
Reglodi D., Illes A., Opper B., Schafer E., Tamas A. and Horvath G. (2018c). Presence and effects of pituitary adenylate cyclase activating polypeptide under physiological and pathological conditions in the stomach. Front. Endocrinol. (Lausanne). 9, 90.
pmcid: PMC5868562
pubmed: 29615974
Reglodi D., Kiss P., Horvath G., Lubics A., Laszlo E., Tamas A., Racz B. and Szakaly P. (2012). Effects of pituitary adenylate cyclase activating polypeptide in the urinary system, with special emphasis on its protective effects in the kidney. Neuropeptides 46, 61-70
pubmed: 21621841
Reglodi D., Vaczy A., Rubio-Beltran E. and MaassenVanDenBrink A. (2018d). Protective effects of PACAP in ischemia. J. Headache Pain 19, 19.
pmcid: PMC5834414
pubmed: 29500688
Richardson S.M., Kalamegam G., Pushparaj P.N., Matta C., Memic A., Khademhosseini A., Mobasheri R., Poletti F.L., Hoyland J.A. and Mobasheri A. (2016). Mesenchymal stem cells in regenerative medicine: Focus on articular cartilage and intervertebral disc regeneration. Methods 99, 69-80
pubmed: 26384579
Sophia Fox A.J., Bedi A. and Rodeo S.A. (2009). The basic science of articular cartilage: structure, composition, and function. Sports Health. 1, 461-468.
pmcid: PMC3445147
pubmed: 23015907
Strange-Vognsen H.H., Arnbjerg J. and Hannibal J. (1997). Immunocytochemical demonstration of pituitary adenylate cyclase activating polypeptide (PACAP) in the porcine epiphyseal cartilage canals. Neuropeptides 31, 137-141.
pubmed: 9179866
Sun Z.P., Wu S.P., Liang C.D., Zhao C.X. and Sun B.Y. (2019a). The synovial fluid neuropeptide PACAP may act as a protective factor during disease progression of primary knee osteoarthritis and is increased following hyaluronic acid injection. Innate Immun. 25, 255- 264.
pmcid: PMC6830887
pubmed: 30935267
Sun B.Y., Sun Z.P., Pang Z.C., Huang W.T. and Wu S.P. (2019b). Decreased synovial fluid pituitary adenylate cyclase-activating polypeptide (PACAP) levels may reflect disease severity in posttraumatic knee osteoarthritis after anterior cruciate ligament injury. Peptides 116, 22-29.
pubmed: 31039374
Szegeczki V., Bauer B., Jüngling A., B.D. Fülöp, Vágó J., Perényi H., Tarantini S., Tamás A., Zákány R., Reglődi D. and Juhász T. (2019). Age-related alterations of articular cartilage in pituitary adenylate cyclase-activating polypeptide (PACAP) gene-deficient mice. GeroScience 41, 775-793.
pmcid: PMC6925077
pubmed: 31655957
Szentléleky E., Szegeczki V., Karanyicz E., Hajdú T., Tamás A., Tóth G., Zákány R., Reglődi D. and Juhász T. (2019). Pituitary adenylate cyclase activating polypeptide (PACAP) reduces oxidative and mechanical stress-evoked matrix degradation in chondrifying cell cultures. Int. J. Mol. Sci. 20, 168.
pmcid: PMC6337298
pubmed: 30621194
Szychlinska M.A., Trovato F.M., Di Rosa M., Malaguarnera L., Puzzo L., Leonardi R., Castrogiovanni P. and Musumeci G. (2016). Coexpression and co-localization of cartilage glycoproteins CHI3L1 and lubricin in osteoarthritic cartilage: Morphological, immunohistochemical and gene expression profiles. Int. J. Mol. Sci. 17, 359.
pmcid: 26978347
pubmed: 26978347
Szychlinska M.A., Stoddart M.J., D'Amora U., Ambrosio L., Alini M. and Musumeci G. (2017). Mesenchymal stem cell-based cartilage regeneration approach and cell senescence: Can we manipulate cell aging and function? Tissue Eng. Part. B. Rev. 23, 529-539.
pubmed: 28514935
Szychlinska M.A., Imbesi R., Castrogiovanni P., Guglielmino C., Ravalli S., Di Rosa M. and Musumeci G. (2019a). Assessment of vitamin D supplementation on articular cartilage morphology in a young healthy sedentary rat model. Nutrients 11, E1260.
pmcid: PMC6628271
pubmed: 31163658
Szychlinska M.A., Castrogiovanni P., Trovato F.M., Nsir H., Zarrouk M., Lo Furno D., Di Rosa M., Imbesi R. and Musumeci G. (2019b). Physical activity and Mediterranean diet based on olive tree phenolic compounds from two different geographical areas have protective effects on early osteoarthritis, muscle atrophy and hepatic steatosis. Eur. J. Nutr. 58, 565-581.
pubmed: 29450729
Tamer T.M. (2013). Hyaluronan and synovial joint: function, distribution and healing. Interdiscip. Toxicology 6, 111-125.
pmcid: PMC3967437
pubmed: 24678248
Toh W.S., Brittberg M., Farr J., Foldager C.B., Gomoll A.H., Hui J.H., Richardson J.B., Roberts S. and Spector M. (2016). Cellular senescence in aging and osteoarthritis. Acta. Orthop. 87, 6-14.
pmcid: PMC5389431
pubmed: 27658487
Tomita M., Reinhold M.I., Molkentin J.D. and Naski M.C. (2002). Calcineurin and NFAT4 induce chondrogenesis. J. Biol. Chem. 277, 42214-42218.
pubmed: 12239209
Toth D., Tamas A. and Reglodi D. (2020). The neuroprotective and biomarker potential of PACAP in human traumatic brain injury. Int. J. Mol. Sci. 21, 827.
pmcid: PMC7037866
pubmed: 32012887
Tsuchida M., Nakamachi T., Sugiyama K., Tsuchikawa D., Watanabe J., Hori M., Yoshikawa A., Imai N., Kagami N., Matkovits A., Atsumi T. and Shioda S. (2014). PACAP stimulates functional recovery after spinal cord injury through axonal regeneration. J. Mol. Neurosci. 54, 380-387.
pubmed: 25074795
Vaudry D., Falluel-Morel A., Bourgault S., Basille M., Burel D., Wurtz O., Fournier A., Chow BK., Hashimoto H., Galas L. and Vaudry H. (2009). Pituitary adenylate cyclase-activating polypeptide and its receptors: 20 years after the discovery. Pharmacol. Rev. 61, 283- 357.
pubmed: 19805477
Wojdasiewicz P., Poniatowski Ł.A. and Szukiewicz D. (2014). The role of inflammatory and anti-inflammatory cytokines in the pathogenesis of osteoarthritis. Mediators Inflamm. 2014, 561459.
pmcid: PMC4021678
pubmed: 24876674
Yang R., Jiang X., Ji R., Meng L., Liu F., Chen X. and Xin Y. (2015). Therapeutic potential of PACAP for neurodegenerative diseases. Cell. Mol. Biol. Lett. 20, 265-278.
pubmed: 26204407
Yoon B.S. and Lyons K.M. (2004). Multiple functions of BMPs in chondrogenesis. J. Cell Biochem. 93, 93-103.
pubmed: 15352166
Zhou C.J., Shioda S., Yada T., Inagaki N., Pleasure S.J. and Kikuyama S. (2002). PACAP and its receptors exert pleiotropic effects in the nervous system by activating multiple signaling pathways. Curr. Protein Pept. Sci.3, 423-439.
pubmed: 12370005