Complex of collagen peptides and glycosaminoglycans: prevention and treatment of diseases of the musculoskeletal system

Cover Page

Cite item

Full Text

Abstract

Disordes of the human musculoskeletal system represent medical problem. Diseases of arthritis, arthrosis of joints, chondrodysplasia of the spine are accompanied by destruction of connective tissues, their structural components: collagen fibrils and proteoglycans. Glycosaminoglycans (chondroprotectors) have been used for a long time to treat arthritis and arthrosis, while collagen peptides (hydrolyzed collagen) are used only in the last 10–15 years to treat joint diseases. Designing the composition of nutraceuticals made of collagen and proteoglycans helps to solve the problem of replenishing missing structural components in the tissues of the musculoskeletal system. We consider that one of promising solutions of this problem is to obtain the complex of collagen peptides and glycosaminoglycans specific for connective tissues. The purpose of this review is to analyze the data available in the literature about collagen peptides, their complexes with glycosaminoglycans and to compare their characteristics with the samples obtained in our studies.

Full Text

Restricted Access

About the authors

T. I. Nikolaeva

Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences

Author for correspondence.
Email: tomivnik@yandex.ru
Russian Federation, Pushchino, Moscow region

K. S. Laurinavichus

Russia bInstitute of Biochemistry and Physiology of Microorganisms, Russian Academy of Sciences

Email: tomivnik@yandex.ru
Russian Federation, Pushchino, Moscow region

M. V. Molchanov

Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences

Email: tomivnik@yandex.ru
Russian Federation, Pushchino, Moscow region

S. M. Kuznetsova

Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences

Email: tomivnik@yandex.ru
Russian Federation, Pushchino, Moscow region

V. I. Emelyanenko

Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences

Email: tomivnik@yandex.ru
Russian Federation, Pushchino, Moscow region

P. V. Shekhovtsov

Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences

Email: tomivnik@yandex.ru
Russian Federation, Pushchino, Moscow region

References

  1. Игнатьева Н.Ю., Аверкиев С.В., Соболь Э.Н., Лунин В.В. Денатурация коллагена II в хрящевой ткани при термическом и лазерном нагреве // Журн. физ. хим. 2005. Т. 79 (8). С. 1505–1513.
  2. Капцов В.В., Русаков Г.Н., Илларионов Ю.А. и др. Лабораторный гомогенизатор. Патент РФ № 2035855. Заявка 06.09.1989. Опубл. 27.05.1995.
  3. Клиническая ревматология / Ред. В.И. Мазуров. СПб.: Фолиант, 2005. 515 с.
  4. Лазерная инженерия хрящей / Ред. В.Н. Багратишвили, Э.Н. Соболь, А.Б. Шехтер. М.: Физматлит, 2006. 488 с.
  5. Николаева Т.И., Тиктопуло Е.И., Ильясова Е.Н., Кузнецова С.М. Структурно-термодинамические аспекты упаковки коллагеновых фибрилл // Биофизика. 2007. Т. 52 (5). С. 899–911.
  6. Николаева Т.И., Кузнецова С.М., Рогачевский В.В. Фибриллообразование коллагена in vitro при температурах, близких к физиологической // Биофизика. 2012. Т. 57. С. 973–981.
  7. Николаева Т.И., Молчанов М.В., Лауринавичюс К.С. и др. Ферментативный гидролиз биополимеров хрящевой ткани под влиянием фитопаина // Междунар. журн. прикл. фунд. иссл. 2015. Т. 12 (7). С. 1252–1256.
  8. Николаева Т.И., Молчанов М.В., Лауринавичюс К.С. и др. Исследование ферментативного гидролиза коллагенов хрящевой ткани // Междунар. журн. прикл. фунд. иссл. 2016. Т. 10 (3). С. 442–447.
  9. Николаева Т.И., Лауринавичюс К.С., Капцов В.В. и др. Разработка комплекса низкомолекулярных пептидов коллагена с гликозаминогликановыми компонентами // Бюл. эксперим. биол. мед. 2018. Т. 165 (5). С. 571–576.
  10. Николаева Т.И., Лауринавичюс К.С., Капцов В.В. и др. Коллагеновые пептиды из гиалиновых хрящей для лечения и профилактики болезней суставов: получение и свойства // Бюл. эксперим. биол. мед. 2019. Т. 167 (2). С. 194–199.
  11. Николаева Т.И., Кузнецова С.М., Емельяненко В.И. и др. Получение коротких пептидов коллагена типа II: температурные условия гомогенизации хрящей и гидролиз коллагена // Бюл. эксперим. биол. мед. 2021. Т. 171 (1). С. 28–31.
  12. Николаева Т.И., Барсук Д.А., Молчанов М.В. и др. Сравнительный анализ степени гидролиза биополимеров в гомогенатах гиалиновых хрящей под воздействием протеолитических ферментов // Биофизика. 2023. Т. 68 (6). С. 1229–1236.
  13. Павлова В.Н., Копьева Т.Т., Слуцкий Л.И., Павлов Г.Г. Хрящ. М.: Медицина, 1988. 318 с.
  14. Пивненко Т.Н., Клычкова Г.Ю., Ковалев Н.Н. и др. Пищевой общеукрепляющий профилактический продукт из хрящевой ткани гидробионтов и способ его получения. Патент РФ № 2250047С1. Опубл. 20.04.2005.
  15. Пивненко Т.Н., Ковалев Н.Н., Запорожец Т.С. Биологически активная добавка к пище “Артрофиш” (в помощь практическому врачу). М.: Академия Естествознания, 2015. 66 с.
  16. Потупчик Т., Веселова О., Эверт Л. и др. Спектр фармакологических эффектов глицина // Врач. 2015. № 12. С. 14–17.
  17. Сова В.В., Попова Н.Д. Способ получения лечебно-профилактической добавки. Патент РФ № 2384342. Заявка 24.11.2008. Опубл. 20.03.2010.
  18. Телишевская Л.Я. Белковые гидролизаты. Получение, состав, применение. М.: Аграрная наука, 2000. 296 с.
  19. Тутельян В.А., Хавинсон В.Х., Малинин В.В. Физиологическая роль коротких пептидов в питании // Бюл. эксп. биол. мед. 2003. Т. 135 (1). С. 1–5.
  20. Хавинсон В.Х., Малинин В.В., Рыжак Г.А. Способ получения средства для поддерживающей терапии, обладающего тканеспецифичной активностью // Патент РФ № 2290936С1. Опубл. 10.01.2007.
  21. Шеховцов П.В. Биологически активная добавка к пище на основе бурых морских водорослей для устранения соединительнотканной недостаточности и укрепления суставно-связочного аппарата. Патент РФ № 2653001С1. Опубл. 04.05.2018.
  22. Ших Е.В. Клинико-фармакологические аспекты применения гидролизованного коллагена второго типа для профилактики и лечения остеоартроза // Фармакол. фармакотер. 2021. № 4. С. 10–18.
  23. Эдсол Д., Гатфренд Х. Биотермодинамика. М.: Мир, 1986. 296 с.
  24. Aghajanian P., Hall S., Wongworawat M.D., Mohan S. The roles and mechanisms of actions of vitamin C in bone: new developments // J. Bone Miner. Res. 2015. V. 30 (11). P. 1945–1955.
  25. Ahmed M., Verma A.K., Patel R. Collagen extraction and recent biological activities of collagen peptides derived from sea-food waste: a review // Sust. Chem. Pharm. 2020. V. 18. P. 315–328.
  26. Aigner T., Stӧve J. Collagens — major component of the physiological cartilage matrix, major target of cartilage degeneration, major tool in cartilage repair // Adv. Drug Deliv. Rev. 2003. V. 55. P. 1569–1593.
  27. Aleman A., Gomez-Guillen M., Montero P. Identification of ACE-inhibitory peptides from squid skin collagen after in vitro gastrointestinal digestion // Food Res. Int. 2013. V. 54 (1). P. 790–795.
  28. Alkayali A. Hydrolysed collagen type II and use thereof. Patent US6025327A. Appl. 2000.02.15. Publ. 2017.08.08.
  29. Ameye L.G., Chee W.S. Osteoarthritis and nutrition. From nutraceuticals to functional foods: a systematic review of the scientific evidence // Arthr. Res. Ther. 2006. V. 8 (4). P. R127.
  30. Anderson J.W., Nicolosi R.J., Borzelleca J.F. Glucosamine effects in humans: a review of effects on glucose metabolism, side effects, safety considerations and efficacy // Food Chem. Toxicol. 2005. V. 43 (2). P. 187–201.
  31. Asari A., Kanemitsu T., Kurihara H. Oral administration of high molecular weight hyaluronan (900 kDa) controls immune system via Toll-like receptor 4 in the intestinal epithelium // J. Biol. Chem. 2010. V. 285 (32). Р. 24751–24758.
  32. Bruyère O., Zegels B., Leonori L. et al. Effect of collagen hydrolysate in articular pain: a 6-month randomized, double-blind, placebo controlled study // Comp. Ther. Med. 2012. V. 20 (3). P. 124–130.
  33. Chen Y., Chen J., Chen J. et al. Recent advances in seafood bioactive peptides and their potential for managing osteoporosis // Crit. Rev. Food Sci. Nutr. 2022. V. 62 (5). P. 1187–1203.
  34. Choudhary A., Sahu S., Vasudeva A. et al. Comparing effectiveness of combination of collagen peptide type I, low molecular weight chondroitin sulfate, sodium hyaluronate and vitamin C versus oral diclofenac sodium in Achilles tendinopathy a prospective randomized control trial // Cureus. 2021. V. 13 (11). P. e19737.
  35. Clark A.G., Rohrbaugh A.L., Otterness I., Kraus V.B. The effects of ascorbic acid on cartilage metabolism in guinea pig articular cartilage explants // Matrix Biol. 2002. V. 21 (2). P. 175–184.
  36. Clark K.L., Sebastianelli W., Flechsenhar K.R. et al. 24-week study on the use of collagen hydrolysate as a dietary supplement in athletes with activity-related joint pain // Curr. Med. Res. Opin. 2008. V. 24. P. 1485–1496.
  37. Elango J., Zamora-Ledezma C., Ge B. et al. Paradoxical duel role of collagen in rheumatoid arthritis: cause of inflammation and treatment // Bioengineering. 2022. V. 9. P. 321–340.
  38. Farì G., Santagati D., Pignatelli G. et al. Collagen peptides, in association with vitamin C, sodium hyaluronate, manganese and copper, as part of the rehabilitation project in the treatment of chronic low back pain // Endocr. Metab. Immune Disord. Drug Targets. 2022. V. 22 (1). P. 108–115.
  39. Fife R.S., Moody S., Houser D., Proctor C. Studies of copper transport in cultured bovine chondrocytes // Biochim. Biophys. Acta. 1994. V. 1201 (1). P. 19–22.
  40. Fox А.J.S., Bedi A., Rodeo A.S. The basic science of articular cartilage: structure, composition, and function // Sports Health. 2009. V. 1 (6). P. 461–468.
  41. Ganini D., Santos J.H., Bonini M.G., Mason R.P. Switch of mitochondrial superoxide dismutase into a prooxidant peroxidase in manganese-deficient cells and mice // Cell Chem. Biol. 2018. V. 25 (4). P. 413–425.
  42. Grover A.K., Samson S.E. Benefits of antioxidant supplements for knee osteoarthritis: rationale and reality // Nutr. J. 2016. V. 15 (1). P. 1–13.
  43. Guillerminet F., Beaupied H., Fabien-Soulé V. et al. Hydrolyzed collagen improves bone metabolism and biomechanical parameters in ovariectomized mice: an in vitro and in vivo study // Bone. 2010. V. 46. P. 827–834.
  44. Hisada N., Satsu H., Mori A. et al. Low-molecular-weight hyaluronan permeates through human intestinal Caco-2 cell monolayers via the paracellular pathway // Biosci. Biotechnol. Biochem. 2008. V. 72. P. 1111–1114.
  45. Hong H., Fan H., Chalamaiah M., Wu J. Preparation of low-molecular-weight, collagen hydrolysates (peptides): current progress, challenges, and future perspectives // Food Сhem. 2019. V. 301. Р. 222–232.
  46. Hong M.-H., Lee J.H., Jung H.S. et al. Biomineralization of bone tissue: calcium phosphate-based inorganics in collagen fibrillar organic matrices // Biomater. Res. 2022. V. 26. P. 42–71.
  47. Kucharz E.J. The collagen: biochemistry and pathophysiology. Berlin: Springer-Verlag, 1992. 430 р.
  48. Lauwers M., Au M., Yuan S., Wen C. COVID-19 in joint ageing and osteoarthritis: current status and perspectives // Int. J. Mol. Sci. 2022. V. 23 (2). P. 720–737.
  49. León-López A., Morales-Peñaloza A., Martínez-Juárez V.M. et al. Hydrolyzed collagen — sources and applications // Molecules. 2019. V. 24 (22). P. 4031–4047.
  50. Lopez H.L. Nutritional interventions to prevent and treat osteoarthritis. Part II: focus on micronutrients and supportive nutraceuticals // PM R. 2012. V. 4. P. S155–S168.
  51. Mobasheri A., Mahmoudian A., Kalvaityte U. et al. A white paper on collagen hydrolyzates and ultrahydrolyzates: potential supplements to support joint health in osteoarthritis? // Curr. Rheumatol. Rep. 2021. V. 23. P. 78–93.
  52. Moskowitz R.W. Role of collagen hydrolysate in bone and joint disease // Semin. Arthr. Rheum. 2000. V. 30. P. 87–99.
  53. Oesser S., Adam M., Babel W., Seifert J. Oral administration of (14)C labeled gelatin hydrolysate leads to an accumulation of radioactivity in cartilage of mice (C57/BL) // J. Nutr. 1999. V. 129. P. 1891–1895.
  54. Oesser S., Seifert J. Stimulation of type II collagen biosynthesis and secretion in bovine chondrocytes cultured with degraded collagen // Cell Tiss. Res. 2003. V. 311. P. 393–399.
  55. Pabst O., Mowat A.M. Oral tolerance to food protein // Mucosal. Immunol. 2012. V. 5. P. 232–239.
  56. Paul C., Leser S., Oesser S. Significant amounts of functional collagen peptides can be incorporated in the diet while maintaining indispensable amino acid balance // Nutrients. 2019. V. 11. P. 1079–1088.
  57. Persikov A.V., Brodsky B. Unstable molecules form stable tissues // PNAS USA. 2002. V. 99 (3). P. 1101–1103.
  58. Porfírio E., Fanaro G.B. Collagen supplementation as a complementary therapy for the prevention and treatment of osteoporosis and osteoarthritis: a systematic review // Rev. Bras. Geriatr. Gerontol. 2016. V. 19 (1). P. 153–164.
  59. Punzi L., Schiavon F., Cavasin F. et al. The influence of intra-articular hyaluronic acid on PGE2 and cAMP of synovial fluid // Clin. Exp. Rheumatol. 1989. V. 7 (3). P. 247–250.
  60. Schadow S., Simons V.S., Lochnit G. et al. Metabolic response of human osteoarthritic cartilage to biochemically characterized collagen hydrolysates // Int. J. Mol. Sci. 2017. V. 18 (1). P. 207–227.
  61. Schunck M., Schulze C.H., Oesser S. P189 collagen hydrolysate supplementation stimulates proteoglycan metabolism and gene expression of articular chondrocytes // Osteoarth. Cartilage. 2007. V. 15. P. B136.
  62. Selvakumar P., Ling T.C., Covington A.D., Lyddiatt A. Enzymatic hydrolysis of bovine hide and recovery of collagen hydrolysate in aqueous two-phase systems // Separ. Purific. Technol. 2012. V. 89. P. 282–287.
  63. Siebert H.C., Burg-Roderfeld M., Eckert T. et al. Interaction of the α2A domain of integrin with small collagen fragments // Protein Cell. 2010. V. 1. P. 393–405.
  64. Skov K., Oxfeldt M., Thøgersen R. et al. Enzymatic hydrolysis of a collagen hydrolysate enhances postprandial absorption rate — a randomized controlled trial // Nutrients. 2019. V. 11. P. 1064.
  65. van Vijven J.P., Luijsterburg P.A., Verhagen A.P. et al. Symptomatic and chondroprotective treatment with collagen derivatives in osteoarthritis: a systematic review // Osteoarthritis Cartilage. 2012. V. 20 (8). P. 809–821.
  66. Walrand S., Chiotelli E., Noirt F. et al. Consumption of a functional fermented milk containing collagen hydrolysate improves the concentration of collagen-specific amino acids in plasma // J. Agric. Food Chem. 2008. V. 56. P. 7790–7795.
  67. Wang L., Wang Q., Liang Q. et al. Determination of bioavailability and identification of collagen peptide in blood after oral ingestion of gelatin // J. Sci. Food Agric. 2015. V. 95. P. 2712–2717.
  68. Zdzieblik D., Brame J., Oesser S. et al. The influence of specific bioactive collagen peptides on knee joint discomfort in young physically active adults: a randomized controlled trial // Nutrients. 2021. V. 13 (2). P. 523.
  69. Zhang J., Jeevithan E., Bao B. et al. Structural characterization, in vivo acute systemic toxicity assessment and in vitro intestinal absorption properties of tilapia (Oreochromis niloticus) skin acid and pepsin solublilized type I collagen // Proc. Biochem. 2016. V. 51. P. 2017–2025.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download
2. Fig. 1. Extracellular matrix of cartilaginous connective tissue. Articular hyaline cartilage contains 10% chondrocytes, 8% collagen, 7% proteoglycans, 75% water (according to: Fox et al., 2009, modified).

Download (356KB)
Indexing metadata
3. Fig. 2. Denaturation of the collagen molecule and breakdown of collagen into low molecular weight peptides.

Download (86KB)
Indexing metadata
4. Fig. 3. Distribution of molecular weights of peptides formed under the influence of caripazim in 33.4 mM K-Na-phosphate buffer, pH 6.0 at 55°C, 10% concentration for 6 h (a) and in imported analogues containing type II collagen hydrolysate: FlexiNovo (Adamed Consumer Healthcare S.A., Polska) (b) and BioCell Collagen II (Now Int., USA) (c). The distribution of molecular weights of peptides characterizes the ratio of the ion mass and the number of ion charges — m/z. Since the ion charge is almost always equal to 1 in MALDI mass spectrometry (MALDI — matrix-assisted laser desorption), the m/z value is considered the ion mass. In this paper, molecular mass data along the X-axis are considered and compared. The magnitude of the ion peak along the Y-axis (intensity) is determined by the relative amount of the ion in the sample.

Download (320KB)
Indexing metadata
5. Fig. 4. A possible mechanism for the supply of components for the biosynthesis of collagen, proteoglycans and the formation of the cartilage matrix is ​​proposed. The amino acids glycine (Gly), proline (Pro), hydroxyproline (Hyp), and hydroxylysine (Hyl) are part of the structure of the collagen triple helix and constitute the main components of the Gly-X-Y triplets. After the collagen molecules are broken down in the gastrointestinal tract to amino acids, dipeptides and tripeptides, they are absorbed, enter the blood, and then into chondrocytes. Dipeptides consist of two amino acid residues, and tripeptides of three. Peptides and molecules synthesized in cells bind near the cell surface, forming the extracellular matrix and cartilage tissue. The destroyed cartilages are replaced by new cartilages.

Download (284KB)
Indexing metadata

Copyright (c) 2024 Russian Academy of Sciences