Osteoarthritis (OA) is the most common degenerative joint disorder worldwide and presents with degradation of articular cartilage, leading to loss of joint mobility and function, accompanied by chronic pain. The chondrocyte/cartilage differentiation status is central in the progression or even cause of OA. However, established and experimental treatment of OA is mainly symptomatic by alleviating pain and interfering with the cartilage degenerative processes to postpone total joint replacement and does not properly address the underlying molecular pathology.

Recently our group completed the screening of BMP-7 peptides and we were successful in identifying BMP-7 mimicking peptides that favourably change the osteoarthritic chondrocyte phenotype towards a healthy phenotype. However, from a cell signaling point-of-view we do not know how the identified BMP-7 mimicking peptides evoke this potential OA disease-modifying activity. In order to understand the molecular mechanism-of-action behind the bioactivity of our BMP-7 peptides on OA chondrocytes we will be investigating this aspect in this particular project. Targeted as well as non-targeted cellular, biochemical, proteomic and transcriptomic approaches will be considered to identify the main molecular route involved in the OA chondrocyte disease-modifying BMP-7 peptide bioactivity.

This PhD-student project builds further on our recent successful identification of BMP-7 mimicking peptide sequences. Potential intra-articular therapeutical use of these peptides for the treatment of OA requires a solid research effort of which the identification of the mechanism-of-action is one. This project will be carried out in the context of other parallel research projects that are running within our group and that are all dedicated to implementing our BMP-7 peptides as potential OA disease-modifying drugs.

The research will be carried out within the Cartilage Molecular Biology group of Dr. T. Welting in the Laboratory for Experimental Orthopedics, department of Orthopedic Surgery, MUMC+. The group has a strong interest and history in chondrocyte molecular biology and is operating in a fully equipped molecular biology lab. Our fundamental molecular research has an important direct connection with the Orthopedic clinic for enabling translational research..

The PhD student will be encouraged to supervise MSc student internships when such opportunities arise.

• The PhD student has finished a master in Biochemistry, Molecular Biology, Molecular Life Sciences or a related master.

• The PhD student has well-developed general molecular biology skills (for example RNA isolation, gene expression, immunoblotting, pull-down/immunoprecipitation), cell culture and nuclei acid transfection skills, experience with bioluminescence techniques, experience with handling bioinformatics datasets and statistical skills. Article 9 animal license will be advantageous.

• The PhD student is socially competent to work in a multidisciplinary team with excellent communication skills.

• The PhD student has a good set of organizational skills.

Some of our relevant publications on this topic:

1. 1.       Ripmeester et al.; Recent insights into the contribution of the changing hypertrophic chondrocyte phenotype in the development and progression of osteoarthritis. Frontiers in Bioengineering and Biotechnology. 2018: Mar 19.
2. 2.       Caron et al.; BAPX-1/NKX3-2 acts as a chondrocyte hypertrophy molecular switch in osteoarthritis. Arthritis and Rheumatology. 2015: Nov;67(11):2944-56.
3. 3.       Caron et al.; Hypertrophic differentiation during chondrogenic differentiation of progenitor cells is stimulated by BMP-2 but suppressed by BMP-7. Osteoarthritis and Cartilage. 2013: Apr;21(4):604-13.

Fixed-term contract: 48 months.

We offer a full-time position within Maastricht University at the Department of Orthopedic Surgery at the Faculty of Health, Medicine and Life Sciences, School CAPHRI  

Temporary employment for 4 years.

Your salary would be € 2.222,- gross per month in the first year up to € 2.840,- gross per month in the fourth year according to the PhD-student salary scale.

Each year an evaluation will take place.

The terms of employment of Maastricht University are set out in the Collective Labour Agreement of Dutch Universities (CAO). Furthermore, local UM provisions also apply.

For more information look at the website www.maastrichtuniversity.nl , Support/UM employees/Employment conditions.

Maastricht University is renowned for its unique, innovative, problem-based learning system, which is characterized by a small-scale and student-oriented approach. Research at UM is characterized by a multidisciplinary and thematic approach, and is concentrated in research institutes and schools. Maastricht University has around 16,300 students and 4,300 employees. Reflecting the university's strong international profile, a fair amount of both students and staff are from abroad. The university hosts 6 faculties: Faculty of Health, Medicine and Life Sciences, Faculty of Law, School of Business and Economics, Faculty of Humanities and Sciences, Faculty of Arts and Social Sciences, Faculty of Psychology and Neuroscience.

http://www.maastrichtuniversity.nl/

Department Orthopaedic Surgery, School CAPHRI

The Department of Orthopaedic Surgery of the Faculty of Health, Medicine and Life Sciences (FHML) of the Maastricht University Medical Center, in Maastricht, the Netherlands has a long-standing clinical expertise in prosthethic treatment of osteoarthritis and regeneration of cartilage defects. The Laboratory for Experimental Orthopedics is a young, enthusiastic and multidisciplinary team with an established specialization in chondrocyte cell biological and –molecular research for the fields of osteoarthritis and skeletal development.

CAPHRI provides high quality multidisciplinary research and teaching aimed at the improvement of the individual's quality of life and the population's health through innovation in public health and health care.

Research and teaching in the School are devoted to contribute to improvements in the area of public health and primary care. CAPHRI focuses on interventions in the chain of care, starting with prevention and primary care, and ending with aftercare and rehabilitation. The aim of the research is to get insight into the effectiveness of interventions, and their adequacy in meeting prospective patients' needs.

http://www.caphri.nl