However, evidence for urinary silicon conservation (to maintain tissue levels), changes in bone/body lengths, bone calcium:phosphorus ratio and differences at the growth plate with silicon deprivation are all novel and deserve further study.
How do these cell- and tissue-level changes emerge in the first place?
Ultimately, understanding the molecular mechanisms that drive tissue-level changes seen in altered development should enable the design of improved cell-based assays that help transcend species differences.
Molecular changes measured in Systems Toxicology studies should, as often as possible, be correlated with cellular or tissue-level changes measured under the same conditions.
The low-dose MIA model, of relatively slow progressing OA, enables in vivo monitoring of tissue-level changes representative of progressive human OA; whereas, in the high-dose model the disease progression is very rapid, which is less suitable for longitudinal monitoring of cartilage and subchondral bone changes.
The idea that cancer derives from a multistep carcinogenesis process, entailing sequential alterations at the molecular level that may underlie tissue-level changes, has gained support from studies on many different cancers (Vogelstein et al, 1988; Sato et al, 1990; Presti et al, 1991).
Therefore, while the potential for thyroid hormones to facilitate cartilage repair is apparent, studies that quantify the tissue-level changes beyond qualitative methods by evaluating the matrix components (that is, collagen and GAG) and functional mechanical properties of repair cartilage are needed.
Furthermore, it is well known that Cryptosporidium infection induces cytoskeletal changes that modulate a localized actin reorganization and channel and transporter insertion, and it is likely that the signaling events that are initiated at the interface between host and pathogens induce whole-cell and, perhaps, tissue-level changes in the cytoskeletal architecture.
Nevertheless, we failed to detect a tissue-level change in Adora1 expression by pain induction or caffeine treatment, indicating that A1 receptors that mediate acupuncture analgesia remained unchanged even after caffeine habituation.
