A recent study 1 from the journal Science Advances analyzed protein turnover that occurs in articular cartilage from lower limb joints in humans. The results showed a potential for regeneration that could likely be exploited to improve joint repair.
What was the Context?
While regeneration exists in certain animal species, humans are believed not to have the ability to counter cumulative damage. In this context, the said type of damage is caused by repetitive joint use as well as certain injuries due to which cartilage breaks down and gives rise to osteoarthritis (OA). According to previous research, the turnover of insoluble collagen in human adult cartilage has been suggested to be quite limited. However, take note, humans do have the limited regenerative capacity. For example, during childhood, the regrowth of distal portions of amputated digits has been observed.
miRNA has been observed to play a significant role in regeneration; however, miRNA’s regenerative role is low in humans. The current study set out to explore the articular cartilage’s protein turnover (in the human lower limb joints).
The Design
The current study collected articular cartilage (as waste surgical specimens) from Duke University Hospital. The full-thickness cartilage was collected from the hip, knee, and ankle joints from patients that had end-stage OA who had undergone total arthroplasty surgery. Take note; the cartilage was from the perilesional regions of the hip, knee, and ankle joint’s load-bearing area.
A total of 18 samples were collected. The samples included three types of joints (hip, knee, and ankle), two types of disease state (healthy as well as OA), and three biological replicates of each type with matched age range. The mean age of healthy non-OA patients was 58.8 years. Their age range was 30 to 82 years. Also, the mean age of the patients with OA was 59.8 years (with the range being 42 and 87 years).
The analysis was performed on a quadrupole Orbitrap benchtop mass spectrometer (Q Exactive) equipped with an EASY-nLC 1000 system. Furthermore, protein identification was performed using the Homo sapiens taxonomy) setting of the Swiss-Prot database with Proteome Discoverer 2.1.
Also, miRNA quantification was done by a real-time polymerase chain reaction. The Deamidation rate was analyzed using the Swiss-PdbViewer.
What were the Results?
The study demonstrated a position-dependent gradient (distal high, proximal low) of protein turnover in human lower limb cartilage. The findings of this study have helped reveal a dynamic anabolic effect in human limbs that showcase a potential (limited) natural regenerative capacity in human cartilage.
According to these results, increased expression of matrix proteins is seen in OA knee cartilage. Also, the higher prevalence of hip and knee OA (compared to ankle OA), might explain the lack of repair in proximal joints.
What was Concluded?
The results suggested the role of regenerative miRNA present in cartilage homeostasis, intrinsic repair capacity, and turnover. Also, the limited regenerative capacity in humans is proposed to be primarily controlled by location rather than the shape of the joint or loading. The use of in vivo protein deamidation molecular clocks helped find a distal-proximal gradient of protein turnover.
The current data also suggested that anabolic treatments may be required in addition to anticatabolic treatments, especially for human hip joints, to prevent or, at least, slow OA’s rate of progression.
The study concluded that more functional studies on the effects of these associated miRNAs would be required to further reveal their regulatory role in cartilage repair and to help prevent certain ailments (including Low Back Pain).
Interestingly, the study suggested that injection of key regenerative miRNA in a joint (either singly or in combination) might have the potential to improve endogenous repair and help resist the degeneration of joint tissues in all types of arthritis.
