Deposition Of Hydroxyapatite Crystals Research Articles

Hydroxyapatite crystal deposition causing rapidly destructive arthropathy of the hip joint

Destructive arthropathy of the hip joint can be attributed to various etiologies like rheumatoid arthritis, aseptic necrosis of the femur head, Charcot's joint, subacute septic arthritis, and tubercular arthritis. A disease that results in much rapid destruction of the hip joint and is not associated with clinical syndrome of above mentioned disease has been reported way back in 1970. However, no evidence-based study has been published to support hydroxyapatite (HA) crystals as a probable cause of rapidly destructive arthropathy of the hip joint. We report a case with microscopic and biochemical confirmation of HA crystal deposition causing destructive arthropathy of the hip joint.

Ectonucleotide Pyrophosphatase/Phosphodiesterase-1 (ENPP1) Protein Regulates Osteoblast Differentiation

ENPP1 (ectonucleotide pyrophosphatase/phosphodiesterase-1) is an established regulator of tissue mineralization. Previous studies demonstrated that ENPP1 is expressed in differentiated osteoblasts and that ENPP1 influences matrix mineralization by increasing extracellular levels of inorganic pyrophosphate. ENPP1 is also expressed in osteoblastic precursor cells when stimulated with FGF2, but the role of ENPP1 in preosteoblastic and other precursor cells is unknown. Here we investigate the function of ENPP1 in preosteoblasts. We find that ENPP1 expression is critical for osteoblastic differentiation and that this effect is not mediated by changes in extracellular concentration levels of phosphate or pyrophosphate or ENPP1 catalytic activity. MC3T3E1(C4) preosteoblastic cells, in which ENPP1 expression was suppressed by ENPP1-specific shRNA, and calvarial cells isolated from Enpp1 knock-out mice show defective osteoblastic differentiation upon stimulation with ascorbate, as indicated by a lack of cellular morphological change, a lack of osteoblast marker gene expression, and an inability to mineralize matrix. Additionally, MC3T3E1(C4) cells, in which wild type or catalytic inactive ENPP1 expression was increased, exhibited an increased tendency to differentiate, as evidenced by increased osteoblast marker gene expression and increased mineralization. Notably, treatment of cells with inorganic phosphate or pyrophosphate inhibited, as opposed to enhanced, expression of multiple genes that are expressed in association with osteoblast differentiation, matrix deposition, and mineralization. Our results indicate that ENPP1 plays multiple and distinct roles in the development of mineralized tissues and that the influence of ENPP1 on osteoblast differentiation and gene expression may include a mechanism that is independent of its catalytic activity.

NLRP3 inflammasome plays a critical role in the pathogenesis of hydroxyapatite-associated arthropathy

The proinflammatory and catabolic cytokine IL-1β has been implicated in the pathogenesis of osteoarthritis (OA) by mediating synovial inflammation and cartilage degeneration. Although synovial macrophages are suggested to be the source of IL-1β, the mechanism remains unclear. Ectopic deposition of hydroxyapatite (HA) crystals in joints is closely associated with OA and other arthropathies, but the precise role of HA in arthritis pathogenesis has not been clearly demonstrated. Here we show that HA crystals of a particular size and shape can stimulate robust secretion of proinflammatory cytokines IL-1β and IL-18 from murine macrophages in a NLRP3 inflammasome-dependent manner. HA-induced inflammasome activation is dependent on potassium efflux, generation of reactive oxygen species (ROS), and lysosomal damage, but independent of cell death. Mice lacking the inflammasome components are protected against HA-induced neutrophilic inflammation in the air-pouch model of synovitis, and they show decreased joint pathology accompanying spontaneous HA deposition in the ank-deficient mouse model of arthritis. Moreover, calcium crystal positive synovial fluids from some OA patients exhibited inflammasome-stimulatory activity in vitro. These results demonstrate that the NLRP3 inflammasome mediates the pathological effect of HA crystals in vitro and in vivo and suggest a critical role for the inflammasome in the pathogenesis of OA.

Acute calcific tendinitis of tibialis posterior tendon (TPT): A rare site of involvement

Calcific tendinitis is a benign inflammatory disorder characterised by deposition of calcium hydroxyapatite crystals in tendons and is commonly seen in tendons around shoulder joint but can also sometimes be encountered in other sites including the hip, wrist, elbow, hand, neck and foot. Calcific tendinitis can clinically mimic many other pathologic entities like infection, gout, myositis ossificans or avulsion fracture which frequently leads to misdiagnosis and inappropriate management. Imaging plays an important role in recognizing and evaluating calcific tendinitis and in differentiating this entity from other pathologic conditions. Calcific tendinitis is largely a self-limiting process which usually responds to conservative treatment although in refractory cases invasive options like steroid injection, needle aspiration or surgery can be considered. Early and accurate diagnosis can prevent needless tests and interventions which the patient may be subjected. We report a case of acute calcific tendinitis involving a rare site (tibialis posterior tendon) with its multimodality imaging appearance.

Intraosseous calcium migration in calcifying tendinitis: a rare cause of single sclerotic injury in the humeral head (2010: 2b)

Intratendinous deposits of hydroxyapatite crystals are very common, particularly in the rotator cuff. In rare cases, the calcium located in the thickness of the supraspinatus tendon can suffer intraosseous migration into the greater tuberosity. We present a case of this rare entity: a 28-year-old patient who attended with pain and functional weakness in the left shoulder. The plain radiograph showed a sclerotic lesion in the greater tuberosity of the humeral head with a radiolucent halo. The MRI showed a lytic lesion containing the calcium inside and associated with an extensive pattern of oedema of the accompanying bone marrow. A plain radiograph taken 6 months before showed a calcifying tendinitis in the thickness of the supraspinatus tendon. A large number of entities can present as single sclerotic lesions of the humeral head. The diagnostic key lies in the existence of the calcifying tendinitis in the earlier study. The treatment of this disease consists of surgical removal of the calcium. The recognition of this entity is important to avoid unnecessary complementary tests and aggressive surgery, given that the surgical treatment is curative and leads to disappearance of the symptoms.

Acute retropharyngeal calcific tendinitis: a case report with unusual location of calcification

Retropharyngeal calcific tendinitis is an inflammatory process caused by calcium hydroxyapatite crystal deposition in the longus colli tendon of the prevertebral space, and it may mimic a retropharyngeal infection or abscess. The diagnosis of retropharyngeal calcific tendinitis will be made radiologically by the detection of calcifications anterior to C1-C3 and prevertebral soft tissue swelling. We present a case of acute retropharyngeal calcific tendinitis with an unusual location of calcification anterior to the C5-C6 disc.

Loss-of-Function ENPP1 Mutations Cause Both Generalized Arterial Calcification of Infancy and Autosomal-Recessive Hypophosphatemic Rickets

The analysis of rare genetic disorders affecting phosphate homeostasis led to the identification of several proteins that are essential for the renal regulation of phosphate homeostasis; for example, fibroblast growth factor 23 (FGF23), which inhibits renal phosphate reabsorption and 1,25-dihydroxyvitamin D synthesis. Here, we report presumable loss-of-function mutations in the ENPP1 gene (ectonucleotide pyrophosphatase/phosphodiesterase) in members of four families affected with hypophosphatemic rickets. We provide evidence for the conclusion that ENPP1 is the fourth gene-in addition to PHEX, FGF23, and DMP1-that, if mutated, causes hypophosphatemic rickets resulting from elevated FGF23 levels. Surprisingly, ENPP1 loss-of-function mutations have previously been described in generalized arterial calcification of infancy, suggesting an as yet elusive mechanism that balances arterial calcification with bone mineralization.

Extensive Calcinosis Cutis in Limited Cutaneous Scleroderma

The CREST syndrome is a subset of limited scleroderma characterized by calcinosis cutis, Raynaud’s phenomenon (RP), esophageal dysmotility, sclerodactyly, and telangiectasias. The calcinosis of skin and soft tissues results from deposition of calcium hydroxyapatite crystals and occurs to a different extent in 20%–40% of patients. The …

Calcific Tendinitis: A Pictorial Review

Calcific tendinitis is caused by the pathologic deposition of calcium hydroxyapatite crystals in tendons and is a common cause of joint pain. The disease typically affects the shoulder and hip, with characteristic imaging findings; however, any joint can be involved. Occasionally, calcific tendinitis can mimic aggressive disorders, such as infection and neoplasm, especially on magnetic resonance imaging. Radiologists should be familiar with the imaging findings to distinguish calcific tendinitis from more aggressive processes. Image-guided percutaneous needle aspiration and steroid injection of calcific tendinitis are useful techniques performed by the radiologist for the treatment of symptomatic cases. Familiarity with these procedures and their imaging appearance is an important aspect in the management of this common disease.

Electrolytic deposition of magnesium-substituted hydroxyapatite crystals on titanium substrate

Electrolytic deposition of magnesium-substituted hydroxyapatite (Mg-HAp) coatings on titanium was investigated and Mg-HAp crystals with up to 2 wt.% Mg 2+ were deposited in electrolytes with various Mg 2+ concentration. The incorporation of Mg substantially changed the morphology of the HAp crystals and decreased the crystal size and crystallinity of the HAp. The similarity with natural dentin and bone in composition and the increased specific surface of the Mg-HAp coatings on the Ti substrates were believed to benefit the bioactivity and the drug-carrying properties of the coatings.

Counterpoint: Hydroxyapatite crystal deposition is not intimately involved in the pathogenesis and progression of human osteoarthritis

The association of hydroxyapatite deposition with osteoarthritis pathogenesis and progression remains controversial, even after decades of study. Hydroxyapatite crystals are found in osteoarthritis in advanced disease only. Even then, hydroxyapatite crystals are found in such small amounts that special analytical techniques are required to detect the crystals. Further, the osteoarthritic joint fluid appears noninflammatory, suggesting that such hydroxyapatite crystals have very small effect on the pathologic process. Formal histopathologic evidence is scant, but hydroxyapatite crystal deposition within osteoarthritic synovium or cartilage is a rare event. Hydroxyapatite crystals may be present at end-stage osteoarthritis, but in insufficient amounts to contribute significantly to osteoarthritis pathogenesis or progression. This review critically examines the evidence from osteoarthritic synovial fluids, imaging, and histopathology to determine whether the well-characterized in vitro cellular reactions to hydroxyapatite apply to the pathogenesis of human osteoarthritis.

Point: Hydroxyapatite crystal deposition is intimately involved in the pathogenesis and progression of human osteoarthritis

The cause of osteoarthritis (OA), the most common form of arthritis, is most likely multifactorial. No drug exists to slow the progression or reverse OA disease progression. Ample data support a key role of calcium-containing crystals, such as hydroxyapatite, in OA pathogenesis. The presence of these crystals, far higher in OA than in any other form of arthritis, correlates with the degree of radiographic degeneration. Calcium-containing crystals have potent biologic effects in vitro that emphasize their pathogenic potential. OA-associated matrix and chondrocyte alterations play an intimate role in the crystal deposition process. A major difficulty has been the lack of a simple technique for crystal identification in affected joints. Enhanced effort is needed to establish calcium-containing crystals as a therapeutic target in OA, as current data suggest an intimate association in its pathogenesis and progression.

Unusual acute crystal-induced hip arthritis: hydroxyapatite deposition of the round ligament

Hydroxyapatite (HA) crystal deposition disease is a common cause of acute inflammatory articular or periarticular pain. Here we report a patient with an acute hip arthritis due to HA crystal deposition of the round ligament. Therefore, HA crystal deposition in periarticular tendons and ligaments of the hip should be added to the differential diagnosis of an acute hip arthritis. Computed tomographic scan may be useful when standard radiographs do not evidence the calcification.

Calcific Tendinitis of Popliteus Tendon: Arthroscopic Excision and Biopsy

Calcific tendinitis results from the deposition of calcium hydroxyapatite crystals in periarticular muscular attachments. It is a rare cause of knee pain commonly affecting patients aged 40 to 70 years. Although commonly seen in the shoulder, it should be kept in mind in nontraumatic cases, particularly when the pain is severe and localized to the lateral aspect of the knee. The exact mechanism of hydroxyapatite deposition is unclear, although genetic and metabolic factors have been suspected. A 45-year-old man presented with severe pain in the lateral aspect of his knee with local tenderness over the lateral epicondyle. Radiographs revealed multiple calcific deposits just below the lateral epicondyle of the femur. Magnetic resonance imaging showed multiple areas of low-signal present intra-articularly near the popliteus tendon that was suspected to be calcification. Erythrocyte sedimentation rate and C-reactive protein were slightly raised and other blood investigations including uric acid were within normal limits. Due to failure of conservative treatment, arthroscopy was performed through standard anteromedial and anterolateral portals. Arthroscopy revealed reddish synovial congestion in the lateral gutter. Partial synovectomy was performed with a shaver through a superolateral portal and the calcific deposit was found to lie between the popliteus tendon and the lateral collateral ligament. This was excised and sent for biopsy. Histopathological evaluation revealed the presence of hydroxyapatite crystals within degenerated tendon thereby confirming the diagnosis of calcific tendinitis. Immediate resolution of symptoms following excision allowed the patient to perform activities of daily living immediately postoperatively without pain.

Retropharyngeal Calcific Tendonitis: Report of Two Cases

Retropharyngeal calcific tendonitis is an inflammatory process of the superior oblique tendons of the longus colli muscle, a neck flexor in the upper cervical spine, caused by deposition of calcium hydroxyapatite crystals; the definitive diagnostic test is computed tomography (CT). Presented in this article are two cases seen at our institution. Patients typically present with acute onset of neck pain/spasm, odynophagia, dysphagia, and/or low grade fevers. Leukocytosis and elevated erythrocyte sedimentation rate may be noted. It is important to understand this entity because its signs and symptoms are mimickers of those of the more serious condition of retropharyngeal space abscess. Calcific tendonitis is managed conservatively whereas retropharyngeal abscess requires incision and drainage. Some may argue that this entity is a zebra because its reported incidence in the literature is low. However, most of these studies were done in an era when CT was not yet in vogue. With today's widespread use of CT and its superb ability to visualize the calcification, the true incidence of this condition is probably higher and, thus, it is important for the family practitioner to be aware of this entity. The astute clinician may save the patient from unnecessary diagnostic workup, undue anxiety, and delays in hospital discharge.

In VitroEffects of Cementum Protein 1 (CEMP1) on Calcium Phosphate Crystal Formation and its Role During the Mineralization Process

ABSTRACTCementum contains specific molecules that could serve to identify, isolate and characterize the cementoblast lineage and to determine the cellular and molecular mechanisms that regulate the cementogenesis process, since it plays a key role during the periodontal regeneration process. One of these molecules is the human cementum protein 1 (CEMP1); which has a molecular weight of 25,9 kDa.In vitroexperiments have shown that CEMP1 promotes cellular adhesion and differentiation. In addition, this protein has been implied in regulating the degree of deposition, composition and morphology of hydroxyapatite crystals formed by putative cementoblastin vitro. Therefore, it is possible that CEMP1 promotes the formation, growth and regulates the morphology of hydroxyapatite crystalsin vitro.We have produced a human recombinant CEMP1 (hrCEMP1) in a prokaryotic system. ThehrCEMP1 purification was realized using the column NiTA HisPrep FF/16. Assays of calcium phosphate crystal growth were realized by means of capillary counterdiffusion system. Our results demonstrated thathrCEMP1 promotes octacalcium phosphate crystal nucleation and possesses high affinity for hydroxyapatite. We infer thathrCEMP1 plays a key role during the regeneration of mineralized tissues.

Amplification of Atherosclerotic Calcification and Mönckeberg's Sclerosis: A Spectrum of the Same Disease Process

Autopsy studies have shown the near universal presence of fatty streaks and fibroatheromas in the general population from which chronic kidney disease (CKD) patients arise. The vast majority of CKD patients have multiple conventional cardiovascular risk factors. Atherosclerosis, once present, can predominantly manifest as medial calcification, which has been previously termed Mönckeberg's sclerosis. This term has also been used in rare cases to describe vascular calcinosis not related to CKD. This clarification is critical to advance the field in terms of pathological diagnosis and treatment of CKD bone and mineral disorder. Factors that appear to promote the osteoblastic transformation of vascular smooth muscle cells and enhance deposition of calcium hydroxyapatite crystals include phosphorus activation of the Pit-1 receptor, bone morphogenic proteins 2 and 4, leptin, endogenous 1,25 dihydroxy vitamin D, vascular calcification activating factor, and measures of oxidative stress. These entities work to accelerate the atherosclerotic process in CKD patients and may be future targets for diagnosis and treatment. Although conventional atherosclerotic risk factors should be optimally managed, it should be noted that trials of hydroxymethylglutaryl-CoA reductase inhibitors have failed to attenuate the rate of progressive vascular calcification as measured by computed tomography scans.

Accelerated Atherosclerotic Calcification and Mo[Combining Diaeresis]nckeberg's Sclerosis

Autopsy studies have demonstrated the near universal presence of fatty streaks and fibroatheromas in the general population from which patients with chronic kidney disease (CKD) arise. The vast majority of patients with CKD have multiple conventional cardiovascular risk factors. Vascular atherosclerotic calcification develops in most patients as they transition from the general population to significant CKD as part of cholesterol crystallization within atherosclerotic lesions. Once present, however, atherosclerotic medial calcification can become prominent and has been previously identified as Mönckeberg's sclerosis. A unifying concept supported by the preponderance of pathologic evidence contends that Mönckeberg's sclerosis is a manifestation of accelerated atherosclerosis in patients with CKD. The term has also been used in rare cases to describe vascular calcinosis not related to CKD. This clarification is critical to advance the field in terms of pathologic diagnosis and treatment of CKD bone and mineral disorder. Factors that seem to promote the osteoblastic transformation of vascular smooth muscle cells and enhance deposition of calcium hydroxyapatite crystals include phosphorus activation of the Pit-1 receptor, bone morphogenic proteins 2 and 4, leptin, endogenous 1,25 dihydroxyvitamin D, vascular calcification activating factor, and measures of oxidative stress. These entities work to accelerate the atherosclerotic process in patients with CKD and may be future targets for diagnosis and treatment because randomized trials with hydroxymethylglutaryl-CoA reductase inhibitors have failed to attenuate the rate of progressive vascular calcification.

Deposition behavior and properties of silk fibroin scaffolds soaked in simulated body fluid

Porous 3D silk fibroin (SF) scaffolds were prepared directly from the SF solution with the addition of methanol and glutaraldehyde by a freeze-drying method. The scaffolds were then soaked in the simulated body fluid (SBF) for the deposition of hydroxyapatite (HA) crystals. The XRD and FTIR results showed that the SF were in β-sheet structure, resulting in the high thermal stability and mechanical properties of scaffolds. The XRD and AAS data revealed that the SF scaffolds could induce the continuous growth and enrichment of HA crystals onto the scaffolds with the extension of soaking time. The mechanical properties of scaffolds increased first with the HA-deposition within 3 d of soaking, then it declined. During the full soaking period, no significant change was observed on the porosity and water-binding ability, which were kept at about 84% and 800%, respectively. The cell cultivation results showed that the scaffolds have the satisfied cell biocompatibility, which was promoted after the HA-deposition. This work suggests that the porous 3D SF scaffolds may be a potential candidate in the bone engineering.

Idiopathic vulvar calcinosis: The counterpart of idiopathic scrotal calcinosis

Calcinosis cutis is characterized by the deposition of hydroxyapatite crystals of calcium phosphate in the skin. It is commonly encountered as a consequence of connective tissue disease or metabolic abnormalities but sometimes could be idiopathic. We report a case of idiopathic calcinosis cutis of the vulva in a healthy woman. A 35-year-old woman presented with multiple asymptomatic yellowish nodules on the external genitalia of one year duration. A few of the nodules broke down spontaneously discharging a chalky white material. She was otherwise healthy and had no systemic complaints. There was neither a history of trauma nor any inflammatory process in the vulvar skin prior to the development of lesions. The hematologic and biochemistry panel such as liver and renal function, serum calcium, phosphorous, electrolytes, uric acid and parathyroid hormone levels were normal. An excision biopsy of the nodule showed features suggestive of calcinosis cutis (Fig. 1). Fig. 1 10× photomicrograph showing the amorphous calcific deposits in the dermis Cutaneous calcification may be divided into four major categories: dystrophic, metastatic, iatrogenic and idiopathic.1 Though dystrophic calcinosis is fairly common, idiopathic calcification is rare, and usually no underlying cutaneous cause can be identified. It commonly presents as painless, firm papules and nodules that appear in childhood and adolescence and gradually increase in number and size. Lesions may be solitary or pedunculated and are initially skin-colored, but as they grow larger they become yellowish and lobulated breaking down spontaneously or when compressed to produce a chalky white material. Microscopic examination typically shows large granular deposits of deeply basophilic material which stains black with Von Kossa stain for calcium.2 The pathogenesis of idiopathic vulvar calcinosis is highly disputed. The principle debate concerning the cause is whether calcium is deposited at the site of inflamed epidermal cysts or whether the calcific nodules are truly idiopathic. Although several authors have suggested that vulvar calcinosis results from dystrophic calcification of the inflammed epidermal cysts, several others have refuted the above facts and found it to be truly idiopathic.3 Idiopathic calcinosis cutis of the vulva is rare with only seven cases reported worldwide. Besides, it has also been reported over the neck after rhytidectomy,4 the sctotal wall5, shaft of the penis6 and the areola of the breast.7 Cornelius et al, have postulated that tiny apatite crystals seen only on electron microscopy in cases of idiopathic calcinosis cutis might act as a source of injury leading to secondary deposition of acid mucopolysaccharides, which become a matrix for crystal formation and calcification. What initiates the deposition of these crystals is not yet known.8 In our case no predisposing cause for calcification could be identified and since the patient was asymptomatic and not keen on surgical removal the lesions were not excised.