Navigation Links
Arthritis: What Wnt wrong?

The cellular signaling protein Wnt, which is involved in embryonic development and cancer, contributes to disease progression of both rheumatoid arthritis and osteoarthritis. The article by Nakamura et al., "Expression profiles and functional analyses of Wnt-related genes in human joint disorders," appears in the July issue of The American Journal of Pathology and is accompanied by a commentary.

Wnt is best known as a proto-oncogene because its disruption can lead to cancer in various organs such as colon, lung, and breast. However, mounting evidence also points to its involvement in arthritic joint disease. Comprehensive analysis of the entire Wnt gene family in the progression of arthritis has been lacking until now.

Researchers at Shinshu University School of Medicine in Nagano, Japan, examined 19 members of the Wnt gene family to determine exactly which of these genes were involved in arthritic joint disease. This extensive study, performed under the direction of Dr. Shigeyuki Wakitani, who is an assistant professor at the Department of Orthopedic Surgery, Shinshu University School of Medicine, examined joint tissue from patients who underwent total knee replacement for rheumatoid arthritis (RA), osteoarthritis (OA), or non-arthritic injury.

Using several molecular methods, Wakitani's group identified Wnt-7b and -10a as genes that were significantly upregulated in the arthritic knee tissues. However, protein expression studies revealed that only Wnt-7b was produced in arthritic joints, with strong protein localization to the synovium (or joint lining) and weak localization to cartilage and bone. In addition, strong Wnt-7b expression most frequently correlated with areas of high inflammation.

The authors also examined whether inflammatory cytokines were produced in primary cartilage and synovial cells from arthritic versus normal joints. While OA cells did not differ from controls, primary RA cells produced TNF-a, IL-1ß and IL-6 at levels 2- to 4-fold above controls. Importantly, this effect could be replicated in normal cells when they were engineered to express Wnt-7b, demonstrating the importance of Wnt-7b in the inflammatory response of RA.

The above findings identify a role for Wnt-7b in arthritic processes. Arthritic diseases manifest differently depending on the type, with RA exhibiting inflammation of the synovium and loss of cartilage and bone and OA exhibiting narrowing of joint space, loss of protective cartilage, and growth of bone cysts (or osteophytes).

Interestingly, Wnt-7b was strongly upregulated within joints at sites of disease manifestation: mainly in synovium of RA but in synovium, cartilage, osteophyte, and bone of OA. In addition, the findings that Wnt-7b was frequently found at sites of inflammation and elicited an inflammatory response are consistent with inflammation as a hallmark of RA disease.

Co-author Dr. Yukio Nakamura is an Orthopedic Surgeon at Shinshu University School of Medicine and is currently at Howard Hughes Medical Institute/Case Western Reserve University as a research associate. Nakamura has been studying the biological activities and signaling pathway of a Wnt-related gene that causes severe joint degenerative disease in humans.

"More specific analyses such as gain-of-function and loss-of-function study of Wnt-7b will give us a clue which Wnt-7b would be an important pathobiological factor in rheumatoid arthritis," added Nakamura. Future studies will investigate the role of Wnt and its signaling partners in arthritic joint destruction. Further delineation of the Wnt signaling pathway in arthritic progression may provide future therapies for the growing number of arthritis suffers.

According to The National Center for Health Statistics, over 42 million US adults, or 20% of the population, complained of arthritic symptoms in 2002.


'"/>

Source:American Journal of Pathology


Related biology news :

1. New comparative toxicogenomics database
2. Measuring the impact of post-genomics on Mediterranean populations
3. Owl genomics presents a HEPATOCHIP for diagnosis of non-alcoholic steatohepatitis
4. Drawing with DNA: Bioart illuminates genomics
5. Study reveals genomics of inflammation from severe injury
6. NIH launches comprehensive effort to explore cancer genomics
7. Environmental metagenomics diagnosing extreme environments, tapping opportunities for clean energy
8. Ticks, flukes, and genomics: Emerging pathogens revealed
9. UC San Diego partners with Venter Institute to build marine microbial genomics cyberinfrastructure
10. Advanced genomics and proteomics improve the diagnosis and treatment of a deadly lung disease
11. Large-scale genomics project will hunt genes behind common childhood diseases
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:4/15/2016)... , April 15, 2016 ... "Global Gait Biometrics Market 2016-2020,"  report to their ... ) , ,The global gait biometrics market ... 13.98% during the period 2016-2020. Gait ... which can be used to compute factors that ...
(Date:3/31/2016)... , March 31, 2016  Genomics firm Nabsys ... founding CEO, Barrett Bready , M.D., who returned ... of the original technical leadership team, including Chief Technology ... of Product Development, Steve Nurnberg and Vice President of ... to the company. Dr. Bready served as ...
(Date:3/22/2016)... and SANDY, Utah , ... which operates the highest sample volume laboratory in ... Genomics and UNIConnect, leaders in clinical sequencing informatics and ... launch of a project to establish the informatics infrastructure ... NSO has been contracted by the Ontario ...
Breaking Biology News(10 mins):
(Date:5/26/2016)... ... May 26, 2016 , ... FireflySci has been manufacturing quartz ... all over the globe. Their cute firefly logo has been spreading to more ... makes spectrophotometer calibration standards that never require recalibration. These revolutionary standards have ...
(Date:5/25/2016)... ... May 25, 2016 , ... The Ankle ... plating options designed to address fractures of the distal tibia and fibula. This ... Acumed Ankle Plating System 3 is composed of seven plate families that span ...
(Date:5/25/2016)... ... ... Scientists at the University of Athens say they have evidence that the ... research that could lead to one good one. Surviving Mesothelioma has just posted an ... The team evaluated 98 mesothelioma patients who got a second kind of ...
(Date:5/25/2016)... ... May 25, 2016 , ... Biohaven Pharmaceutical Holding ... has granted the company’s orphan drug designation request covering BHV-4157 for the treatment ... by the FDA. , Spinocerebellar ataxia is a rare, debilitating neurodegenerative disorder ...
Breaking Biology Technology: