Distinctiveness of Femoral and Acetabular Mesenchymal Stem and Progenitor Populations in Patients with Primary and Secondary Hip Osteoarthritis Due to Developmental Dysplasia.

Primary hip osteoarthritis (pOA) develops without an apparent underlying reason, whereas secondary osteoarthritis arises due to a known cause, such as developmental dysplasia of the hips (DDH-OA). DDH-OA patients undergo total hip arthroplasty at a much younger age than pOA patients (50.58 vs. 65 years in this study). Recently, mesenchymal stem and progenitor cells (MSPCs) have been investigated for the treatment of osteoarthritis due to their immunomodulatory and regenerative potential. This study identified cells in subchondral bone expressing common MSPC markers (CD10, CD73, CD140b, CD146, CD164, CD271, GD2, PDPN) in vivo and compared the proportions of these populations in pOA vs. DDH-OA, further correlating them with clinical, demographic, and morphological characteristics. The differences in subchondral morphology and proportions of non-hematopoietic cells expressing MSPC markers were noted depending on OA type and skeletal location. Bone sclerosis was more prominent in the pOA acetabulum (Ac) in comparison to the DDH-OA Ac and in the pOA Ac compared to the pOA femoral head (Fh). Immunophenotyping indicated diagnosis-specific differences, such as a higher proportion of CD164+ cells and their subsets in DDH-OA, while pOA contained a significantly higher proportion of CD10+ and GD2+ cells and subsets, with CD271+ being marginally higher. Location-specific differences showed that CD271+ cells were more abundant in the Fh compared to the Ac in DDH-OA patients. Furthermore, immunohistochemical characterization of stromal bone-adjacent cells expressing MSPC markers (CD10, CD164, CD271, GD2) in the Ac and Fh compartments was performed. This research proved that immunophenotype profiles and morphological changes are both location- and disease-specific. Furthermore, it provided potentially effective targets for therapeutic strategies. Future research should analyze the differentiation potential of subsets identified in this study. After proper characterization, they can be selectively targeted, thus enhancing personalized medicine approaches in joint disease management.

Specificities in the Structure of the Cartilage of Patients with Advanced Stages of Developmental Dysplasia of the Hip.

Developmental dysplasia of the hip (DDH) presents varying degrees of femoral head dislocation, with severe cases leading to the formation of a new articular surface on the external side of the iliac bone-the neoacetabulum. Despite conventional understanding suggesting otherwise, a tissue resembling hyaline cartilage is found in the neoacetabulum and acetabulum of Crowe III and IV patients, indicating a potential for hyaline cartilage development without mechanical pressure. To test this theory, acetabular and femoral head cartilage obtained from patients with DDH was stained with hematoxylin-eosin and toluidine blue. The immunohistochemical analysis for collagen types II and VI and aggrecan was performed, as well as delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) analysis on a 7.0 T micro-MRI machine. The results obtained from DDH patients were compared to those of the control groups. Hyaline cartilage was found in the neoacetabulum and the acetabulum of patients with DDH. The nature of the tissue was confirmed with both the histological and the MRI analyses. The results of this study proved the presence of hyaline cartilage in patients with DDH at anatomical regions genetically predisposed to be bone tissue and at regions that are not subjected to mechanical stress. This is the first time that the neoacetabular cartilage of patients with advanced stages of DDH has been characterized in detail.

Novel micro-MRI approach for subchondral trabecular bone analysis in patients with hip osteoarthritis is comparable to micro-CT approach.

AIM: To test the agreement between a newly developed micro-magnetic resonance imaging (MRI) analysis of the subchondral bone and the micro-computed tomography (CT) approach. METHODS: Samples obtained from 10 patients with osteoarthritis undergoing total hip arthroplasty were scanned with a 7.0 T micro-MRI. Proton density-weighted images and proton density-weighted images with fat suppression were obtained. The results were validated with a micro-CT device. Micro-MRI and micro-CT scans of the same sample were aligned, and regions of interest were delineated on equal areas of the sample. Bone volume fraction was calculated by using in-house plugins. The agreement between the methods was tested with Bland-Altman analysis. RESULTS: The agreement between the methods was good, with average difference of 2.167%. The differences between the methods were not significant (P=0.272, t test). CONCLUSION: The novel micro-MRI approach could be used for subchondral bone analysis. With further optimization for clinical MRI machines, the approach can be also used in the diagnostics of hip osteoarthritis.

Current knowledge on the genetic background of developmental dysplasia of the hip and the histomorphological status of the cartilage.

Developmental dysplasia of the hip (DDH) represents a morphological abnormality characterized by the incongruity of femoral head and acetabulum. It ranges from mild dysplastic changes to complete dislocation. DDH has been associated with several hereditary and environmental risk factors, which could explain the incidence variability among different countries. Numerous genes may be involved in the disease etiology and progression. However, there are controversies in the literature regarding some of these genes. DDH-induced secondary osteoarthritis (OA) is characterized by changes in the macromolecule content of the cartilage and the expression of cartilage degradation markers. In addition, it exhibits a pattern of specific histological changes, with several reported differences between primary and DDH-induced secondary OA. The articular cartilage of patients with DDH shows specific radiological characteristics, including changes visible already in infancy, but also at pre-arthritic stages, early stages of OA, and in fully developed DDH-induced secondary OA. Although DDH has been extensively researched in different disease stages, the etiology of the disorder still remains uncertain. This review focuses on the current knowledge on the histomorphological status of the cartilage and the genetic background of DDH.

The neoacetabulum in developmental dysplasia of the hip is covered with hyaline cartilage.

The lack of adequate mechanical stimulation and appropriate contact between acetabulum and femoral head results with developmental dysplasia of the hip (DDH). In DDH, hip joint forms normally during the organogenesis, but deforms during the fetal development. Acetabulum remains comparable in width with normal acetabulum, but has increased length and decreased depth, resulting in a poor coverage of the femoral head. In cases of severe hip subluxation and luxation due to DDH, the femoral head articulates with the external side of the iliac bone, forming a neoacetabulum in the position that was genetically predetermined to become bony tissue. A neoacetabulum is therefore formed under intermittent mechanical pressure, but never has the depth of a physiological acetabulum due to different forces at this new location. Over time, the depth of the neoacetabulum increases, and a crest is formed that obstructs reposition of the femoral head into the anatomic acetabulum. We hypothesize that the neoacetabulum on the iliac bone in DDH patients is formed of hyaline cartilage, despite the lack of genetic predisposition for hyaline cartilage formation in this area. We assume that as the femoral head migrates during development in such patients, joint capsular tissue interposes between the external side of the iliac bone and the femoral head, and a cartilaginous metaplasia of the capsule follows. This results in elongation of the acetabular cartilage in the same direction as the femoral head migrated. This assumption is based on the finding that in patients with hip luxation such interposed joint capsule showed signs of cartilaginous transformation. Furthermore, in the inner part of such joint capsules, proteoglycan production was notably higher than that of other non-cartilaginous tissue. Also, high expression of cartilaginous genes, which are usually not expressed in this tissue, was observed. Confirmation of this hypothesis would put a new perspective on the pathogenesis of DDH and could lead to better management or even prevention of this condition.