Naturally Expressed and Recombinant Human Lubricin:
Scientific Background and Collaboration Opportunity
Lubricin, also known as proteoglycan 4 (PRG4), superficial zone protein (SZP), and megakaryocyte stimulating factor (MSF), is a glycoprotein that has several biological functions. First, Lubricin, as the name suggests, acts like a lubricant and contributes to the lowering of friction in joints and cartilage. The Lubricin is both bound to the cells as well as in solution and both aid in reducing friction. Second, other than protecting cells from wear degradation, Lubricin has been found to have cytoprotective properties by preventing cellular adhesion. Third, Lubricin plays a role in regulating the cartilage surface and matrix binding. Fourth, Lubricin has a chondroprotective feature since it provides synovial fluid with an ability to dissipate strain energy induced by mammalian locomotion.1 These properties of Lubricin provide for quite a few therapeutic possibilities.
Lubricin is one of the three molecules responsible for joint lubrication. Research has shown that a decrease in lubricin synthesis and lower levels of lubricin results in loss of joint lubrication, which an early step in arthritis development.2, 3 A continuation of this research has shown that the addition of recombinant lubricin to a rat model of osteoarthritis (OA) resulted in the recombinant lubricin binding to the cartilage surfaces, which significantly reduced the cartilage degeneration.4 This means that the addition of recombinant lubricin has great potential in treating OA and other similar diseases such as rheumatoid arthritis (RA), camptodactyly-arthropathy-coxa vara-pericarditis syndrome (CACP).5
Research has also shown that it takes time for changes in lubricin concentration to develop in OA. Both the no OA and mild OA groups had very similar lubricin concentrations while the lubricin concentration level was significantly lower in moderate OA group.6
The addition of recombinant lubricin results in some of the lubricin binding to the cartilage while some goes into solution. Both the bound and soluble lubricin have mechanisms that aid in lowering the friction of the cartilage.7 Further research has shown that lubricin binds through the C-terminal end of the molecule 8, which allows for the central mucin domain to form a low friction, surface protecting layer.9
Lubricin’s role in improving tendon gliding has also been studied. While adding lubricin alone fails to have an impact on the tendon gliding resistance, the addition of cd-gelatin plus lubricin significantly lowered the gliding resistance of the tendons. This research can aid in improving the gliding ability of tendon grafts done clinically.10,11
While adding recombinant lubricin is one method for improving the health of patients, another option is influencing the cytokines known to regulate the synthesis of lubricin. It has been found that both transforming growth factor beta (TGF-b1) and BMP-7 synthesize lubricin 12 while interleukin 1 (IL-1) and tumor necrosis factor alpha (TNF-a) both reduce the production of lubricin.13
It has also been found that lubricin has harmful properties in cartilage repair. Due to Lubricin’s ability to lubricate, lubricin impairs cartilage-cartilage integration, which blocks the ability of cartilage fissures to heal.14,15 A removal of some lubricin might allow for the healing of torn cartilage. Another most unfortunate side effect of lubricin is the possibility that lubricin is linked to prosthesis loosening.16
SBH Sciences is offering highly pure naturally expressed and recombinant human lubricin with a molecular weight of 206 kDa measured by sedimentation analysis, yet due the post-translational modifications the apparent molecular weight on SDS-PAGE is 280-345 kDa.
SBH Sciences is the sole producer of these products for the R&D market. We are looking for partners to investigate human lubricin as therapeutics agent, as well as a diagnostic tool.
We are open for suggestions and would be pleased to hear from you.
1. Jay GD et al, Proceeding of the National Academy of Sciences of the USA, 104 (15) 6194-9, Apr 2007.
2. Elsaid KA, Jay GD et al, Arthritis and Rheumatism, 56(1) 108-16, Jan 2007.
3. Jay GD et al, Arthritis and Rheumatism, 56(11) 3662-9, Nov 2007.
4. Flannery CR et al, Arthritis and Rheumatism, 60 (3) 840-7, Mar 2009.
5. Bao JP et al, Molecular Biology Reports, 2010.
6. Teeple E, Jay GD et al, Journal of Orthopaedic Research, 26(2) 231-7, Feb 2008.
7. Gleghorn JP et al, Journal of Orthopaedic Research, 27(6) 771-7, Jun 2009.
8. Jones AR et al, Journal of Orthopaedic Research, 25(3) 283-92, Mar 2007.
9. Zappone B, Jay GD et al, Langmuir, 24(4) 1495-1508, Feb 2008.
10. Taguchi M, Jay GD et al, The Journal of Bone and Joint Surgery, 90(1) 129-35, Jan 2008.
11. Taguchi M, Jay GD et al, The Journal of Hand Surgery, 34(7) 1276-81 Sep 2009.
12. Lee SY et al, Biochemical and Biophysical Research Communications, 376(1) 148-53, Nov 2008.
13. Jones AR and Flannery CR, European Cells & Materials, 13 40-45, Mar 2007.
14. Schaefer DB, Jay GD et al, Biorheology, (41-3,4) 503-8, 2004.
15. Funakoshi T et al, Clinical Orthopaedics and Related Research, 468(6) 1588-99, Jun 2010.
16. Morawietz L et al, Virchows Archiv, 443(1) 57-66. Jul 2003.