Collagen Hydrolysates: A Source of Bioactive Peptides Derived from Food Sources for the Treatment of Osteoarthritis
Abstract
:1. Introduction: Osteoarthritis
1.1. Joint Tissues
1.1.1. Cartilage
1.1.2. Bone
1.2. Cellular Changes in OA Joints; Inflammation
1.3. OA Treatments
2. Nutritional Supplementation: Collagen Hydrolysates
2.1. Collagen
2.2. Collagen Hydrolysates
2.3. Bioactivity and Health Benefits of CHs
2.3.1. Clinical Studies on CHs and CH-Derived Peptides
2.3.2. In Vitro and Animal Studies on CHs and CH-Derived Peptides
3. Digestion and Bioavailability of CHs and CH-Derived Peptides
3.1. Gastrointestinal Digestion
3.2. Absorption and Hepatic First Pass: Bioavailability of CHs and CH-Derived BAPS
3.3. In Vitro Models of Digestion and Absorption
3.3.1. Digestion
3.3.2. Absorption and First-Pass Metabolism
4. Microbial Effects of Non-Digested and Unabsorbed CH Components
5. Future Trends
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Zhang, Y.; Jordan, J.M. Epidemiology of osteoarthritis. Clin. Geriatr. Med. 2010, 26, 355–369. [Google Scholar] [CrossRef] [PubMed]
- Peat, G.; Thomas, M.J. Osteoarthritis year in review 2020: Epidemiology & therapy. Osteoarthr. Cartil. 2021, 29, 180–189. [Google Scholar] [CrossRef]
- Vina, E.R.; Kwoh, C.K. Epidemiology of osteoarthritis: Literature update. Curr. Opin. Rheumatol. 2018, 30, 160–167. [Google Scholar] [CrossRef]
- Van Spil, W.E.; Kubassova, O.; Boesen, M.; Bay-Jensen, A.-C.; Mobasheri, A. Osteoarthritis phenotypes and novel therapeutic targets. Biochem. Pharmacol. 2019, 165, 41–48. [Google Scholar] [CrossRef]
- Hunter, D.J.; March, L.; Chew, M. Osteoarthritis in 2020 and beyond: A Lancet Commission. Lancet 2020, 396, 1711–1712. [Google Scholar] [CrossRef]
- Lim, Y.Z.; Hussain, S.M.; Cicuttini, F.M.; Wang, Y. Chapter 6: Nutrients and Dietary Supplements for Osteoarthritis. In Bioactive Food as Dietary Interventions for Arthritis and Related Inflammatory Diseases, 2nd ed.; Watson, R.R., Preedy, V.R., Eds.; Elsevier Inc.: Amsterdam, The Netherlands; Academic Press: Cambridge, MA, USA, 2019; pp. 97–137. [Google Scholar]
- Veronese, N.; Cooper, C.; Reginster, J.-Y.; Hochberg, M.; Branco, J.; Bruyère, O.; Chapurlat, R.; Al-Daghri, N.; Dennison, E.; Herrero-Beaumont, G.; et al. Type 2 diabetes mellitus and osteoarthritis. Semin. Arthritis Rheum. 2019, 49, 9–19. [Google Scholar] [CrossRef] [PubMed]
- Eymard, F.; Parsons, C.; Edwards, M.H.; Petit-Dop, F.; Reginster, J.Y.; Bruyère, O.; Richette, P.; Cooper, C.; Chevalier, X. Diabetes is a risk factor for knee osteoarthritis progression. Osteoarthr. Cartil. 2015, 23, 851–859. [Google Scholar] [CrossRef]
- Singh, G.; Miller, J.D.; Lee, F.H.; Pettitt, D.; Russell, M.W. Prevalence of cardiovascular disease risk factors among US adults with self-reported osteoarthritis: Data from the Third National Health and Nutrition Examination Survey. Am. J. Manag. Care 2002, 8, S383–S391. [Google Scholar]
- Baudart, P.; Louati, K.; Marcelli, C.; Berenbaum, F.; Sellam, J. Association between osteoarthritis and dyslipidaemia: A systematic literature review and meta-analysis. RMD Open 2017, 3, e000442. [Google Scholar] [CrossRef]
- Sellam, J.; Berenbaum, F. Is osteoarthritis a metabolic disease? Joint Bone Spine 2013, 80, 568–573. [Google Scholar] [CrossRef]
- Kluzek, S.; Newton, J.L.; Arden, N.K. Is osteoarthritis a metabolic disorder? Br. Med. Bull. 2015, 115, 111–121. [Google Scholar] [CrossRef]
- Castañeda, S.; Vicente, E.F. Osteoarthritis: More than Cartilage Degeneration. Clin. Rev. Bone. Miner. Metab. 2017, 15, 69–81. [Google Scholar] [CrossRef]
- Loeser, R.F.; Goldring, S.R.; Scanzello, C.R.; Goldring, M.B. Osteoarthritis: A disease of the joint as an organ. Arthritis Rheum. 2012, 64, 1697–1707. [Google Scholar] [CrossRef] [PubMed]
- Sophia Fox, A.J.; Bedi, A.; Rodeo, S.A. The basic science of articular cartilage: Structure, composition, and function. Sports Health 2009, 1, 461–468. [Google Scholar] [CrossRef] [PubMed]
- León-López, A.; Morales-Peñaloza, A.; Martínez-Juárez, V.M.; Vargas-Torres, A.; Zeugolis, D.I.; Aguirre-Álvarez, G. Hydrolyzed Collagen-Sources and Applications. Molecules 2019, 24, 4031. [Google Scholar] [CrossRef] [PubMed]
- Daneault, A.; Prawitt, J.; Fabien Soulé, V.; Coxam, V.; Wittrant, Y. Biological effect of hydrolyzed collagen on bone metabolism. Crit. Rev. Food Sci. Nutr. 2017, 57, 1922–1937. [Google Scholar] [CrossRef] [PubMed]
- Stewart, H.L.; Kawcak, C.E. The Importance of Subchondral Bone in the Pathophysiology of Osteoarthritis. Front. Vet. Sci. 2018, 5, 178. [Google Scholar] [CrossRef] [PubMed]
- Elango, J.; Sanchez, C.; de Val, J.E.M.S.; Yve, H.; Wang, S.; Motaung, K.S.C.M.; Guo, R.; Wang, C.; Robinson, J.; Regenstein, J.M.; et al. Cross-talk between primary osteocytes and bone marrow macrophages for osteoclastogenesis upon collagen treatment. Sci. Rep. 2018, 8, 5318. [Google Scholar] [CrossRef]
- Nedeva, I.R.; Vitale, M.; Elson, A.; Hoyland, J.A.; Bella, J. Role of OSCAR Signaling in Osteoclastogenesis and Bone Disease. Front. Cell Dev. Biol. 2021, 9, 641162. [Google Scholar] [CrossRef]
- Park, D.R.; Kim, J.; Kim, G.M.; Lee, H.; Kim, M.; Hwang, D.; Lee, H.; Kim, H.-S.; Kim, W.; Park, M.C.; et al. Osteoclast-associated receptor blockade prevents articular cartilage destruction via chondrocyte apoptosis regulation. Nat. Commun. 2020, 11, 4343. [Google Scholar] [CrossRef] [PubMed]
- Liu, J.; Zhang, B.; Song, S.; Ma, M.; Si, S.; Wang, Y.; Xu, B.; Feng, K.; Wu, J.; Guo, Y. Bovine collagen peptides compounds promote the proliferation and differentiation of MC3T3-E1 pre-osteoblasts. PLoS ONE 2014, 9, e99920. [Google Scholar] [CrossRef]
- Min, G.; He, M.; Kaili, L.; Yantao, H.; Xuehong, C.; Chunbo, W. Collagen Hydrolysate Gly-Pro-Hyp on Osteoblastic Proliferation and Differentiation of MC3T3-E1 Cells. J. Clin. Nurs. Res. 2017, 1, 40–46. [Google Scholar] [CrossRef]
- Amarasekara, D.S.; Kim, S.; Rho, J. Regulation of Osteoblast Differentiation by Cytokine Networks. Int. J. Mol. Sci. 2021, 22, 2851. [Google Scholar] [CrossRef]
- Liu, Q.; Li, M.; Wang, S.; ** our knowledge to create healthier and more sustainable foods. Food Funct. 2020, 11, 9397–9431. [Google Scholar] [CrossRef] [PubMed]
- Punt, A.; Peijnenburg, A.; Hoogenboom, R.; Bouwmeester, H. Non-animal approaches for toxicokinetics in risk evaluations of food chemicals. ALTEX 2017, 34, 501–514. [Google Scholar] [CrossRef]
- Chen, L.; Shen, X.; **a, G. Effect of Molecular Weight of Tilapia (Oreochromis Niloticus) Skin Collagen Peptide Fractions on Zinc-Chelating Capacity and Bioaccessibility of the Zinc-Peptide Fractions Complexes In Vitro Digestion. Appl. Sci. 2020, 10, 2041. [Google Scholar] [CrossRef]
- Guo, L.; Harnedy, P.A.; Zhang, L.; Li, B.; Zhang, Z.; Hou, H.; Zhao, X.; FitzGerald, R.J. In Vitro assessment of the multifunctional bioactive potential of Alaska pollock skin collagen following simulated gastrointestinal digestion. J. Sci. Food Agric. 2015, 95, 1514–1520. [Google Scholar] [CrossRef] [PubMed]
- Alemán, A.; Gómez-Guillén, M.C.; Montero, P. Identification of ace-inhibitory peptides from squid skin collagen after in vitro gastrointestinal digestion. Food Res. Int. 2013, 54, 790–795. [Google Scholar] [CrossRef]
- Larder, C.E.; Iskandar, M.M.; Sabally, K.; Kubow, S. Complementary and efficient methods for di- and tri-peptide analysis and amino acid quantification from simulated gastrointestinal digestion of collagen hydrolysate. LWT 2022, 155, 112880. [Google Scholar] [CrossRef]
- Feng, M.; Betti, M. Transepithelial transport efficiency of bovine collagen hydrolysates in a human Caco-2 cell line model. Food Chem. 2017, 224, 242–250. [Google Scholar] [CrossRef]
- Larder, C.E.; Iskandar, M.M.; Kubow, S. Assessment of Bioavailability after In Vitro Digestion and First Pass Metabolism of Bioactive Peptides from Collagen Hydrolysates. Curr. Issues Mol. Biol. 2021, 43, 113. [Google Scholar] [CrossRef]
- Shigemura, Y.; Nakaba, M.; Shiratsuchi, E.; Suyama, M.; Yamada, M.; Kiyono, T.; Fukamizu, K.; Park, E.Y.; Nakamura, Y.; Sato, K. Identification of food-derived elastin peptide, prolyl-glycine (Pro-Gly), in human blood after ingestion of elastin hydrolysate. J. Agric. Food Chem. 2012, 60, 5128–5133. [Google Scholar] [CrossRef]
- Kawaguchi, T.; Nanbu, P.N.; Kurokawa, M. Distribution of prolylhydroxyproline and its metabolites after oral administration in rats. Biol. Pharm. Bull. 2012, 35, 422–427. [Google Scholar] [CrossRef]
- Bello, A.E.; Oesser, S. Collagen hydrolysate for the treatment of osteoarthritis and other joint disorders:a review of the literature. Curr. Med. Res. Opin. 2006, 22, 2221–2232. [Google Scholar] [CrossRef] [PubMed]
- Oesser, S.; Adam, M.; Babel, W.; Seifert, J. Oral administration of 14C labeled gelatin hydrolysate leads to an accumulation of radioactivity in cartilage of mice (C57/BL). J. Nutr. 1999, 129, 1891–1895. [Google Scholar] [CrossRef] [PubMed]
- Wang, L.; Wang, Q.; Qian, J.; Liang, Q.; Wang, Z.; Xu, J.; He, S.; Ma, H. Bioavailability and Bioavailable Forms of Collagen after Oral Administration to Rats. J. Agric. Food Chem. 2015, 63, 3752–3756. [Google Scholar] [CrossRef]
- Taga, Y.; Kusubata, M.; Ogawa-Goto, K.; Hattori, S. Identification of Collagen-Derived Hydroxyproline (Hyp)-Containing Cyclic Dipeptides with High Oral Bioavailability: Efficient Formation of Cyclo(X-Hyp) from X-Hyp-Gly-Type Tripeptides by Heating. J. Agric. Food Chem. 2017, 65, 9514–9521. [Google Scholar] [CrossRef]
- Sontakke, S.B.; Jung, J.H.; Piao, Z.; Chung, H.J. Orally Available Collagen Tripeptide: Enzymatic Stability, Intestinal Permeability, and Absorption of Gly-Pro-Hyp and Pro-Hyp. J. Agric. Food Chem. 2016, 64, 7127–7133. [Google Scholar] [CrossRef]
- Lea, T. Caco-2 Cell Line. In The Impact of Food Bioactives on Health: In Vitro and Ex Vivo Models; Verhoeckx, K., Cotter, P., López-Expósito, I., Kleiveland, C., Lea, T., Mackie, A., Requena, T., Swiatecka, D., Wichers, H., Eds.; Springer: Cham, Switzerland, 2015; pp. 103–111. [Google Scholar]
- Song, H.; Tian, Q.; Li, B. Novel Hyp-Gly-containing antiplatelet peptides from collagen hydrolysate after simulated gastrointestinal digestion and intestinal absorption. Food Funct. 2020, 11, 5553–5564. [Google Scholar] [CrossRef]
- Larregieu, C.A.; Benet, L.Z. Drug discovery and regulatory considerations for improving in silico and in vitro predictions that use Caco-2 as a surrogate for human intestinal permeability measurements. Am. Assoc. Pharm. Sci. J. 2013, 15, 483–497. [Google Scholar] [CrossRef]
- Takenaka, T.; Harada, N.; Kuze, J.; Chiba, M.; Iwao, T.; Matsunaga, T. Human small intestinal epithelial cells differentiated from adult intestinal stem cells as a novel system for predicting oral drug absorption in humans. Drug Metab. Dispos. 2014, 42, 1947–1954. [Google Scholar] [CrossRef]
- Takenaka, T.; Harada, N.; Kuze, J.; Chiba, M.; Iwao, T.; Matsunaga, T. Application of a human intestinal epithelial cell monolayer to the prediction of oral drug absorption in humans as a superior alternative to the Caco-2 cell monolayer. J. Pharm. Sci. 2016, 105, 915–924. [Google Scholar] [CrossRef] [PubMed]
- Pászti-Gere, E.; Pomothy, J.; Jerzsele, Á.; Pilgram, O.; Steinmetzer, T. Exposure of human intestinal epithelial cells and primary human hepatocytes to trypsin-like serine protease inhibitors with potential antiviral effect. J. Enzym. Inhib. Med. Chem. 2021, 36, 659–668. [Google Scholar] [CrossRef]
- Zhao, X.; Xu, X.X.; Liu, Y.; **, E.Z.; An, J.J.; Tabys, D.; Liu, N. The in vitro protective role of bovine lactoferrin on intestinal epithelial barrier. Molecules 2019, 24, 148. [Google Scholar] [CrossRef]
- Bretschneider, B.; Brandsch, M.; Neubert, R. Intestinal transport of beta-lactam antibiotics: Analysis of the affinity at the H+/peptide symporter (PEPT1), the uptake into Caco-2 cell monolayers and the transepithelial flux. Pharm. Res. 1999, 16, 55–61. [Google Scholar] [CrossRef] [PubMed]
- Cheng, K.C.; Li, C.; Hsieh, Y.; Montgomery, D.; Liu, T.; White, R.E. Development of a high-throughput in vitro assay using a novel Caco-2/rat hepatocyte system for the prediction of oral plasma area under the concentration versus time curve (AUC) in rats. J. Pharmacol. Toxicol. Methods 2006, 53, 215–218. [Google Scholar] [CrossRef]
- Lau, Y.Y.; Chen, Y.H.; Liu, T.T.; Li, C.; Cui, X.; White, R.E.; Cheng, K.C. Evaluation of a novel in vitro Caco-2 hepatocyte hybrid system for predicting in vivo oral bioavailability. Drug Metab. Dispos. 2004, 32, 937–942. [Google Scholar]
- Zhang, M.; Xu, J.; Wang, T.; Wan, X.; Zhang, F.; Wang, L.; Zhu, X.; Gao, P.; Shu, G.; Jiang, Q.; et al. The dipeptide Pro-Gly promotes IGF-1 expression and secretion in HepG2 and female mice via PepT1-JAK2/STAT5 Pathway. Front. Endocrinol. 2018, 9, 424. [Google Scholar] [CrossRef] [PubMed]
- Schott, E.M.; Farnsworth, C.W.; Grier, A.; Lillis, J.A.; Soniwala, S.; Dadourian, G.H.; Bell, R.D.; Doolittle, M.L.; Villani, D.A.; Awad, H.; et al. Targeting the gut microbiome to treat the osteoarthritis of obesity. JCI Insight 2018, 3, e95997. [Google Scholar] [CrossRef]
- Rowland, I.; Gibson, G.; Heinken, A.; Scott, K.; Swann, J.; Thiele, I.; Tuohy, K. Gut microbiota functions: Metabolism of nutrients and other food components. Eur. J. Nutr. 2017, 57, 1–24. [Google Scholar] [CrossRef] [PubMed]
- Liu, X.; Zeng, B.; Zhang, J.; Li, W.; Mou, F.; Wang, H.; Zou, Q.; Zhong, B.; Wu, L.; Wei, H.; et al. Role of the Gut Microbiome in Modulating Arthritis Progression in Mice. Sci. Rep. 2016, 6, 30594. [Google Scholar] [CrossRef]
- Ashaolu, T.J.; Ashaolu, J.O. Prebiotic peptides, their formation, fermentation in the gut, and health implications. Biotechnol. Prog. 2021, 37, e3142. [Google Scholar] [CrossRef]
- Mobasheri, A.; Mahmoudian, A.; Kalvaityte, U.; Uzieliene, I.; Larder, C.E.; Iskandar, M.M.; Kubow, S.; Hamdan, P.C.; de Almeida, C.S.; Favazzo, L.J.; et al. A White Paper on Collagen Hydrolyzates and Ultrahydrolyzates: Potential Supplements to Support Joint Health in Osteoarthritis? Curr. Rheumatol. Rep. 2021, 23, 78. [Google Scholar] [CrossRef] [PubMed]
Study Design | Population | Supplement Used and Details | Reference |
---|---|---|---|
Randomized double-blind, placebo-controlled | Knee OA | Colnatur by Ordesa (Eberbach, Germany) CH with a mean molecular weight of 3500 Da. Sourced from “traceable non-ruminant bones of neutral taste and odour” Improvement in knee joint pain | Benito-Ruiz et al., (2009) [51] |
Single-center, prospective, randomized, double-blind, placebo-controlled | Postmenopausal women with reduced bone mineral density | FORTIBONE® by Gelita Described as a mixture of specific bioactive collagen peptides (SCP) with a mean molecular weight of ~5 kDa. However, peptides were not given. Fortibone is derived from Type I and III bovine collagen Increased bone mineral density | König et al., (2018) [52] |
Randomized, double-blind, placebo-controlled | Knee, hip, elbow, shoulder, hand, and/or lumbar spine OA | Genacol AminoLock Collagen Source: Bovine collagen. No additional details in the manuscript. Reduced VAS scores | Bruyère et al., (2012) [53] |
Randomized, double-blind, placebo-controlled | Knee OA | Porcine (supplied by NittaGelatin Inc., Osaka, Japan) and bovine (Nitta Gelatin India Ltd., Panampilly Nagar, India) CH-derived peptides. Peptide sequences not given. Reduced WOMAC and VAS scores | Kumar et al., (2015) [54] |
Randomized, double-blind, placebo-controlled study | Elderly sarcopenic men | BODYBALANCE by Gelita using bovine type 1 collagen. Increased fat-free mass, bone mass, and muscle mass | Zdzieblik et al., (2015) [55] |
Monocentric, prospective, randomized, double-blind, placebo-controlled | Athletes with knee pain | FORTIGEL by Gelita; described as a mixture of collagen peptides. Sequences not given. Decreased activity-related pain intensity | Zdzieblik et al., (2017) [56] |
Triple-blind, placebo-controlled, randomized controlled trial | Knee pain | Genacol AminoLock Collagen Source: Bovine collagen. No additional details in the manuscript. Improvement in various joint structures | Feliciano et al., (2017) [57] |
Prospective, randomized, placebo-controlled, double-blind study | Athletes with activity-related joint pain | CH-Alpha from Gelita. No details given. Diminished joint discomfort and pain | Clark et al., (2008) [58] |
Single-center, prospective, randomized, placebo-controlled, double-blind, pilot trial | Mild knee OA | FORTIGEL by Gelita; described as a mixture of collagen peptides. Sequences not given. Increased proteoglycan content in knee cartilage and improved cartilage morphology | McAlindon et al., (2011) [59] |
Randomized double-blind study | Pre-pubertal Spanish children | Gelatine Royal (Kraft Foods Europe, Barcelona, Spain), unspecified collagen source. Improved bone remodelling during growth | Martin-Bautista et al., (2011) [60] |
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Larder, C.E.; Iskandar, M.M.; Kubow, S. Collagen Hydrolysates: A Source of Bioactive Peptides Derived from Food Sources for the Treatment of Osteoarthritis. Medicines 2023, 10, 50. https://doi.org/10.3390/medicines10090050
Larder CE, Iskandar MM, Kubow S. Collagen Hydrolysates: A Source of Bioactive Peptides Derived from Food Sources for the Treatment of Osteoarthritis. Medicines. 2023; 10(9):50. https://doi.org/10.3390/medicines10090050
Chicago/Turabian StyleLarder, Christina E., Michèle M. Iskandar, and Stan Kubow. 2023. "Collagen Hydrolysates: A Source of Bioactive Peptides Derived from Food Sources for the Treatment of Osteoarthritis" Medicines 10, no. 9: 50. https://doi.org/10.3390/medicines10090050