TABLE 1.
Vitamins and minerals absent in DMEM [and therefore defined chondrogenic media (Kean and Dennis, 2015)].
| Component | Role in chondrogenesis | Normal range1 | References |
| Chromium | Unknown, has a role in insulin/glucose metabolism | 0.3–28 μg/L | Finch, 2015 |
| Cobalt | Unknown, required for vitamin B12 and other enzymes | 0.0–0.9 μg/L | Mobasheri et al., 2006; MayoClinic, 2016 |
| Copper | Part of lysyl oxidase complex – collagen crosslinking | 90–670 μg/L | Makris et al., 2013a; Finch, 2015 |
| Iodine | Deficiency causes cartilage defects | 40–92 μg/L | Ren et al., 2007; MayoClinic, 2016 |
| Manganese | Deficiency results in skeletal abnormalities | 0.6–12 μg/L | Finch, 2015 |
| Molybdenum | Unknown | 0.3–2.0 μg/L | Sardesai, 1993; MayoClinic, 2016 |
| α-linolenic acid | Unknown, precursor of phospholipid membrane | 2.8–54 mg/L | Connor, 1999; MayoClinic, 2016 |
| Thyroxine2 | Enhances and stimulates terminal differentiation | 9–17 ng/L | Mello and Tuan, 2006; MayoClinic, 2016; Whitney et al., 2018 |
| Vitamin A | Shown to inhibit chondrogenesis | 113–780 μg/L | Pacifici et al., 1980; Lind et al., 2013; Masuda et al., 2015; MayoClinic, 2016 |
| Vitamin B7 | Unknown | 57–3004 ng/L | Ren et al., 2007; MayoClinic, 2016 |
| Vitamin B12 | Unknown, deficiency causes growth retardation | 180–914 ng/L | Stabler, 2013; MayoClinic, 2016 |
| Vitamin D | Implicated in chondrogenesis | 24–86 ng/L | Tsonis, 1991; MayoClinic, 2016 |
| Vitamin E | Unknown | 3.8–18.4 mg/L | Wluka et al., 2002; MayoClinic, 2016 |
| Vitamin K | Possible role in early chondrogenesis | 0.1–2.2 μg/L | Barone et al., 1991; Booth, 1997; MayoClinic, 2016 |
| Zinc | Stimulates chondrocyte growth and collagen production | 0.6–1.2 mg/L | Koyano et al., 1996; Litchfield et al., 1998 |
1Normal reference range in blood or serum; synovial fluid is not regularly assessed for these components. Defined chondrogenic media is supplemented with vitamin C and ITS + Premix which contains selenium and linoleic acid, thus providing three essential vitamins and minerals absent in DMEM. 2Thyroxine, although a growth factor, was included because of our previous study showing upregulation of type II collagen (Whitney et al., 2018).