Osteoarthritis (OA) is a progressive degenerative disease that contributes to more than $140 billion in medical expenditures annually (Murphy, Costernas, Pasta, Helmick, and Yelin 2017). Recent data suggest OA affects approximately 12% of the U.S. population between the ages of 25 and 74 (Cisternas, Murphy, Sacks, Solomon, Pasta, and Helmick 2016).

This disease is a joint ailment that involves the cartilage and many of its surrounding tissues. The most common joints affected are knees, hips, hands, facet joints, and feet (Litwic, Edwards, Dennison, and Cooper 2013). These represent several types of synovial joints, which are characterized by a joint cavity that contains synovial fluid. The bone ends of these kinds of joints are covered with articular cartilage, which is a thin layer of hyaline cartilage, a metabolic form of Teflon. Synovial fluid is a lubricant that reduces friction between the articular cartilage (Zhang, Egan, and Wang 2015). The knee joint is a hinge joint that is stabilized by exterior and internal ligaments; the flexion and extension movements are softened by synovial fluid, several types of bursae, and an infrapatellar fat pad.

OA is inflammation of the joint, typically characterized by pain, swelling, stiffness, and reduced mobility. During the joint degeneration process, the articular cartilage wears down and there is increased production of synovial fluid. While the standard of care involves intake of medications to relieve pain and inflammation, some interventions may include gene therapy and possibly joint replacement surgery or arthroplasty (Walsh, Mapp, and Kelly 2015). Dietary interventions may include the consumption of collagen and gelatin as well as their respective hydrolysates (Liu, Nikoo, Boran, Zho, and Regenstein 2015) and possibly glucosamine and chondroitin (Fransen, Agaliotis, Naim, et al. 2015; Clegg, Reda, Harris, et al. 2006; Henrotin, Mobasheri and Marty 2012).

Collagens are unique structural proteins and represent the most abundant proteins (~30%) in the human body. These proteins have vital functions in maintaining the integrity of skeletal muscle and are critical in the growth and development of muscle tissue (McCormick 2009). There are nearly 30 types of collagen among vertebrates and invertebrates that are products of more than 30 genes (Gordon and Hahn 2010). The helical structure of collagen is dominated (>10%) by the amino acid sequences of glycine, proline, and hydroxyproline. The hydroxylation of proline is a post-translational process in the collagenous domains via a family of propyl 3-hydroxylases (Hudson and Eyre 2013; Pokidysheva, Boudko, Vranka, et al. 2014). Irreversibly hydrolyzed collagen is gelatin, which is used in the food, medical, and pharmaceutical industries.

Consuming collagen and gelatin has been advocated to improve joint health, bone strength, and skin wellness, and has gained popularity in the functional foods category. The hydrolysates and the respective peptides may have biological activities, which may reflect the purported beneficial effects of these substances. Several studies among animal models indicate that as much as 70%–90% of the low molecular weight (nearly 15 kDa) gelatin hydrolysate peptides may be absorbed based on the accumulation of radioactive proline (Oesser, Adam, Babel, and Seifert 1999; Watanabe-Kamiyama, Shimizu, Kamiyama, et al. 2010).

Several small, short-term studies with collagen hydrolysates fed to humans suggest some symptoms associated with OA may be reduced (Schauss, Stenehjem, Park, Endres, and Clewell 2012; Benito-Ruiz, Camacho-Zambrano, Carillo-Arcentales, et al. 2009). More than a dozen small studies of marine gelatin hydrolysates and their respective peptides demonstrated biological activities in model systems (Liu, Nikoo, Boran, Zhou, and Regenstein 2015).

It is interesting to note that rat intestine enterocytes produce proline-specific carboxypeptidases, which may be important in the digestion of proline-containing peptides and proteins such as collagen and gelatin (Erickson, Song, Yoshioka, Gulli, Miura, and Kim 1989). In part, these findings are consistent with kidney Pro-X carboxypeptidases that can hydrolyze several Pro-X dipeptides, whereas these enzymes do not recognize Pro–Pro, Pro–Hyp, Hyp–Gly, and Pro–Leu bonds (Hiraoka 2004). However, these specific enterocyte-derived enzymes have not been identified in humans.

There are a limited number of studies that suggest some microflora, such as specific bifidobacteria, probionibacteria, and yeast, produce exopeptidases that exhibit proline-specific activities (Quelen, Dupuis, and Boyaval 1995; Minagawa, Kaminogawa, Tsukasaki, Motoshima, and Yamauchi 1985; Bolumar, Sanz, Aristoy, and Toldra 2003). These studies reinforce our understanding of the amino acid composition of collagen, which is dominated by proline. Like any other structural and ubiquitous protein, the uniqueness of its digestibility and its hydrolysates by humans must be investigated rigorously, especially with respect to managing OA.




Roger ClemensRoger Clemens, DrPH, CFS,
Contributing Editor
Adjunct Professor, Univ. of Southern California’s School of Pharmacy, Los Angeles, Calif.
[email protected]