Osteoarthritis
Osteoarthritis is a degenerative joint disease that is characterised by cartilage loss, subchondral bone remodelling, and osteophytosis. Clinically there may be variable reduced range of motion, swelling, and joint pain.
Pathology
- See also: Synovial Joints, Fibrous Connective Tissues
The extracellular matrix of cartilage is made up of two main macromolecules: type II collagen and aggrecan. Aggrecan is a large aggregating proteoglycan which retains water. The type II collagen provides intrinsic resistance to tension, and allows the proteoglycans to swell against it to provide resistance to compression. There are other more minor components that also play a role in matrix structure such as other forms of collagen (e.g. types IX, XI, and VI collagen), proteoglycans (e.g. biglycan, decorin), and cartilage oligomerix matrix protein.
In the normal state there is an equilibrium between synthesis and degradation of the extracellular matrix. Degradation allows for clearing of old components so that fresh components can be synthesised. In osteoarthritis there is a disruption of this balance so that the degradative processes are favoured, leading to cartilage destruction.
The classic degradative enzymes, produced in the chondrocyte and synovium, are the metalloproteinases (MMPs) which facilitate the turnover of the extracellular matrix in both normal and osteoarthritic states. It is thought that MMP-1 is the primary collagenase in rheumatoid arthritis, and MMP-13 is the primary collagenase in osteoarthritis. The role of MMP-1 may be distinct in each joint, being elevated in knee osteoarthritis, and reduced in hip osteoarthritis. MMP-3 on the other hand is reduced in osteoarthritis, and elevated in rheumatoid arthritis. There are various other changes in MMP expression in osteoarthritis.[1]
The A Disintegrin And Metalloproteinase with Thrombospondin Motifs (ADAMTS) group of proteinases were discovered later and are involved in both the synthesis and degradation of the extracellular matrix. ADAMTS enzymes include the procollagen propeptidases (ADAMTS-2, -3, and -14) that are involved in collagen biosynthesis, and the aggrecanases (ADAMTS-1, -4, -5, -9, and -15) that are involved in aggrecan degradation. There are various changes seen in osteoarthritis with the expression and activity of these proteinases.[2]
There are also important inhibitors, and the tissue inhibitors of metalloproteinases (TIMPs) are able to inhibit the activity of MMPs and potentially ADAMTS. In osteoarthritis there can be an imbalance between metalloproteinase and TIMP activities.[1]
In viewing changes in the expression of various genes, it is important to remember that such changes don't necessarily mean that a particular enzyme is causative in the pathogenesis of osteoarthritis. There may be different factors involved across the spectrum of osteoarthritis from mild to end-stage.[2]
Cartilage oligomerix protein (COMP) is also known as thrombospondin 5. It's exact function remains unclear but it appears to be an important regulator of extracellular matrix assembly and stabilisation of the matrix through interacting between collagen fibrils and matrix components. It appears to be a marker of cartilage turnover and has been studied as both a diagnostic and prognostic indicator of osteoarthritis.[3]
Risk Factors
Important risk factors include genetic predisposition, increasing age, obesity, abnormal biomechanics, joint overload, and previous joint injury. Joint injury can alter the mechanical loading of the joint, which can lead activation of catabolic pathways.
There is important explicit evidence in lumbar disc degeneration through the studies of twins. Biomechanical factors in this setting only account for some of the variance, while larger proportions are due to genetic factors.[4] These genetic factors confer a predisposition but do not in themselves guarantee the development of degenerative changes.
Relationship to Pain
In the spine, zygapophyseal joints can be a source of pain, but there is no correlation between radiological osteoarthritis and pain. Osteoarthritis is more common with age regardless of pain.
In the lumbar spine. there is no difference in the grade of arthropathy between painful and non-painful zygapophyseal joints as determined by controlled intra-articular blocks. Similarly there is a clinically insignificant correlation between back pain and lumbar degenerative disc changes, with such changes not being related to pain the majority of the time.[5]
References
- ↑ 1.0 1.1 Kevorkian L, Young DA, Darrah C, Donell ST, Shepstone L, Porter S, Brockbank SM, Edwards DR, Parker AE, Clark IM. Expression profiling of metalloproteinases and their inhibitors in cartilage. Arthritis Rheum. 2004 Jan;50(1):131-41. doi: 10.1002/art.11433. PMID: 14730609.
- ↑ 2.0 2.1 Yang, C-Y et al. “ADAMTS and ADAM metalloproteinases in osteoarthritis - looking beyond the 'usual suspects'.” Osteoarthritis and cartilage vol. 25,7 (2017): 1000-1009. doi:10.1016/j.joca.2017.02.791
- ↑ Tseng, Susan et al. “Cartilage Oligomeric Matrix Protein (COMP): A Biomarker of Arthritis.” Biomarker insights vol. 4 33-44. 17 Feb. 2009, doi:10.4137/bmi.s645
- ↑ Battié MC, Videman T, Kaprio J, Gibbons LE, Gill K, Manninen H, Saarela J, Peltonen L. The Twin Spine Study: contributions to a changing view of disc degeneration. Spine J. 2009 Jan-Feb;9(1):47-59. doi: 10.1016/j.spinee.2008.11.011. PMID: 19111259.
- ↑ Bogduk N. Degenerative joint disease of the spine. Radiol Clin North Am. 2012 Jul;50(4):613-28. doi: 10.1016/j.rcl.2012.04.012. PMID: 22643388.
