Identification of novel genetic variations affecting osteoarthritis patients.

BACKGROUND: Osteoarthritis (OA) is a progressive joint disease characterized by gradual degradation of extracellular matrix (ECM) components in the cartilage and bone. The ECM of cartilage is a highly specified structure that is mainly composed of type II collagen and provides tensile strength to the tissue via aggrecan and proteoglycans. However, changes in the ECM composition and structure can lead to loss of collagen type II and network integrity. Several risk factors have been correlated with OA including age, genetic predisposition, hereditary factors, obesity, mechanical injuries, and joint trauma. Certain genetic association studies have identified several genes associated with OA using genome-wide association studies (GWASs). RESULTS: We identified several novel genetic variants affecting genes that function in several candidate causative pathways including immune responses, inflammatory and cartilage degradation such as SELP, SPN, and COL6A6. CONCLUSIONS: The approach of whole-exome sequencing can be a promising method to identify genetic mutations that can influence the OA disease.

Derivation and differentiation of bone marrow mesenchymal stem cells from osteoarthritis patients.

Osteoarthritis (OA) of the knee is a degenerative joint disease caused by the progressive reduction of the articular cartilage surface that leads to reduced joint function. Cartilage degeneration occurs through gradual loss in extracellular matrix components including type II collagen and proteoglycan. Due to limited inherent self repair capacity of the cartilage, the use of cell-based therapies for articular cartilage regeneration is considered promising. Bone marrow mesenchymal stem cells (BM-MSCs) are multipotent cells and are highly capable of multilineage differentiation which render them valuable for regenerative medicine. In this study, BM-MSCs were isolated from OA patients and were characterized for MSC specific CD surface marker antigens using flowcytometry and their differentiation potential into adipocytes, osteocytes and chondrocytes were evaluated using histological and gene expression studies. BM-MSCs isolated from OA patients showed short spindle shaped morphology in culture and expressed positive MSC related CD markers. They also demonstrated positive staining with oil red O, alizarin red and alcian blue following differentiation into adipocytes, osteocytes and chondrocytes, respectively. In addition, chodrogenic related genes such as collagen type II alpha1, cartilage oligomeric matrix protein, fibromodulin, and SOX9 as well as osteocytic related genes such as alkaline phosphatase, core-binding factor alpha 1, osteopontin and RUNX2 runt-related transcription factor 2 were upregulated following chondrogenic and osteogenic differentiation respectively. We have successfully isolated and characterized BM-MSCs from OA patients. Although BM-MSCs has been widely studied and their potential in regenerative medicine is reported, the present study is the first report in our series of experiments on the BMSCs isolated from OA patients at King Abdulaziz University Hospital, Jeddah, Saudi Arabia.

Incidence and potential causative factors associated with chronic benign neutropenia in the Kingdom of Saudi Arabia.

BACKGROUND: Benign neutropenia often presents in certain populations without any genotype nor phenotype. Middle East countries are among the regions where endemic cases of chronic benign neutropenia are reported in the general population with an incidence of approximately between 10-15%. Not many studies have been performed to ascertain the cause or burden associated with this condition. The objective of the current study was to identify the frequency and characterize the consequences of chronic benign neutropenia in the country of Saudi Arabia. RESULTS: Benign neutropenia was found to be high in the Saudi Arabia general population (up to 20%), with an average neutrophil count of 1.48 (range 0.99 - 1.95 × 10(9)cells/L), with Saudis having a higher incidence of chronic benign neutropenia compared to non-Saudis (p = <0.05). Complete blood count analyses showed significant difference in the total white cell count of neutrophils (p < 0.0001), WBC (p < 0.0001), lymphocytes (p < 0.001), monocytes (p < 0.001), eosinophils (p = 0.013) as well as the CD19 B cells (p = 0.008). CONCLUSIONS: Our study is the first to carefully quantitate benign neutropenia in Saudi Arabia. We identified that this condition is prevalent in the middle aged population (18 years to 55 years). These individuals not only had lower neutrophil counts, but also reduced peripheral blood cells types, especially the B-lymphocyte population (CD19 subset). As B-lymphocytes are involved in antibody production and antigen recognition, a decrease might easily predispose the individuals to infectious agents. As such more mechanistic studies need to be undertaken to understand the cause and potential long-term consequences of benign neutropenia.