The Relationship between Vitamin K and Osteoarthritis: A Review of Current Evidence

Abstract

Vitamin K is a cofactor of γ-glutamyl carboxylase, which plays an important role in the activation of γ-carboxyglutamate (gla)-containing proteins that negatively regulate calcification. Thus, vitamin K status might be associated with osteoarthritis (OA), in which cartilage calcification plays a role in the pathogenesis of the disease. This review collates the evidence on the relationship between vitamin K status (circulating or dietary intake level of vitamin K, or circulating uncarboxylated gla proteins) and OA from human observational studies and clinical trial, to examine its potential as an agent in preventing OA. The current literature generally agrees that a sufficient level of vitamin K is associated with a lower risk of OA and pathological joint features. However, evidence from clinical trials is limited. Mechanistic study shows that vitamin K activates matrix gla proteins that inhibit bone morphogenetic protein-mediated cartilage calcification. Gla-rich proteins also inhibit inflammatory cascade in monocytic cell lines, but this function might be independent of vitamin K-carboxylation. Although the current data are insufficient to establish the optimal dose of vitamin K to prevent OA, ensuring sufficient dietary intake seems to protect the elderly from OA.

The Role of Vitamin K in Humans: Implication in Aging and Age-Associated Diseases

“…Since VKDPs, including MGP, Gla-rich protein (GRP), periostin, and OC, were detected in cartilage and bone, VK may have a protective role in OA and joint health [79]. Thus, sufficient dietary VK intake and/or supplementation seemed to protect the population from age-related musculoskeletal diseases [80].…”

Vitamin K-Dependent Proteins in Skeletal Development and Disease

“…Later vitamin K uptake was shown to be inversely related to bone fracture and osteoporosis risk and vitamin K has been demonstrated to promote bone formation and suppress bone resorption [19,37,38]. Moreover, Vitamin K has also been associated with osteoarthritis and rheumatoid arthritis [39][40][41][42].…”

“…Vitamin K has been shown to ameliorate experimental arthritis in the rat. This effect has been suggested to be mediated by vitamin-K-dependent inhibition of synovial hyperplasia and is considered to be independent of VDKPs [41]. In inflammatory arthritis synovial fibroblast-like cells (SFLCs) exhibit increased proliferation and less apoptosis in response to inflammatory signals.…”

“…Thus, they form a pannus-like tissue, infiltrating the joint space and secreting further pro-inflammatory cytokines on the one hand, and matrix-degrading enzymes on the other hand [45,46]. Vitamin K has been suggested to enhance apoptosis of FLSCs in inflamed joints [41]. This effect is most likely independent of VKDPs.…”

Characterization of dynamic changes in Matrix Gla Protein (MGP) gene expression as function of genetic risk alleles, osteoarthritis relevant stimuli, and the vitamin K inhibitor warfarin

“…As such, low vitamin K levels have been hypothesized to play a role in OA pathogenesis (14,15). Similarly, J o u r n a l P r e -p r o o f vitamin K antagonists such as warfarin, that are frequently prescribed for the prevention of thromboembolic events in patients with atrial fibrillation (16), have been suggested to predispose to OA (17). Nonetheless, the direct effect of warfarin on human articular cartilage tissue homeostasis has not been assessed.…”